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Eficacia de los inhibidores de la enzima convertidora de angiotensina (ECA) sobre la disminución de la presión arterial para la hipertensión primaria

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Referencias

References to studies included in this review

Ir a:

Applegate 1996 {published data only}

Applegate WB, Cohen JD, Wolfson P, Davis A, Green S. Evaluation of blood pressure response to the combination of enalapril (single dose) and diltiazem ER (four different doses) in systemic hypertension. American Journal of Cardiology 1996;78:51‐5.

Belz 1986 {published data only}

Belz GG, Lange H, Tschollar W, Neis W. Cilazapril in essential hypertension: A placebo‐controlled double‐blind study to establish the dosage [Cilazapril bei essentieller hypertonie: Eine placebokontrollierte doppelblindstudie zur dosisfindung]. Medizinische Klinik 1986;81(15‐16):524‐9.

Black 1997 {published data only}

Black HR, Graff A, Shute D, Stoltz R, Ruff D, Levine J, Shi Y, Mallows S. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin‐converting enzyme inhibitor, lisinopril. Journal of Human Hypertension 1997;11(8):483‐9.

Boeijinga 1993 {published data only}

Boeijinga JK, Kraaij CJ, Kleinbloesem H, Cohen AF, Breimer DD. The influence of cilazapril on anticoagulants in hypertensive patients treated with coumarins. Current Therapeutic Research 1993;54(4):443‐51.

Brown 1990 {published data only}

Brown CL, Backhouse CI, Grippat JC, Santoni JP. The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin‐angiotensin system in hypertensive subjects. European Journal of Clinical Pharmacology 1990;39(4):327‐32.

Carlsen 1995 {published data only}

Carlsen JE, Buchmann M, Hoglund C, Pellinen T, Honkanen T, Soerensen OH, Leth A, Maltbaek N. 24‐hour antihypertensive effect of oral cilazapril? A placebo‐controlled study evaluating 1, 2.5 and 5 mg once daily. Clinical Drug Investigation 1995;10(4):221‐7.

Chan 1997 {published data only}

Chan P, Lin CN, Tomlinson B, Lin TH, Lee YS. Additive effects of diltiazem and lisinopril in the treatment of elderly patients with mild‐to‐moderate hypertension. American Journal of Hypertension 1997;10(7):743‐9.

Chrysant 1993 {published data only}

Chrysant SG, McDonald RH, Wright JT, Barden PL, Weiss RJ. Perindopril as monotherapy in hypertension: A multicenter comparison of two dosing regimens. Archives of Internal Medicine 1993;53(4):479‐84.

Chrysant 1994 {published data only}

Chrysant S. Antihypertensive effectiveness of low‐dose lisinopril‐hydrochlorothiazide combination. Archives of Internal Medicine 1994;154(7):737‐43.

Chrysant 1996 {published data only}

Chrysant SG, Fagan T, Glazer R, Kriegman A. Effects of benazepril and hydrochlorothiazide, given alone and in low‐ and high‐dose combinations, on blood pressure in patients with hypertension. Archives of Family Medicine 1996;5(1):17‐24.
Fagan T, Head K, DeSilva J, Whalen J. Double‐blind comparison of once daily benazepril, hydrochlorothiazide and placebo in mild to moderate hypertension. American Journal of Hypertension 1989;2(5, Part 2):78A.
Gomez HJ. Dose‐response studies with benazepril in mild to moderate hypertension. Clinical Cardiology 1991;14(Suppl IV):IV‐22‐7.

Cushman 1998 {published data only}

Cushman WC, Cohen JD, Jones RP, Marbury TC, Rhoades RB, Smith LK. Comparison of the fixed combination of enalapril/diltiazem ER and their monotherapies in stage 1 to 3 essential hypertension. American Journal of Hypertension 1998;11(1):23‐30.

De Bruijn 1994 {published data only}

De Bruijn JHB, Orofiamma BA, Pauly NC. Efficacy and tolerability of trandolapril (0.5‐2 mg) administered for 4 weeks in patients with mild‐to‐moderate hypertension. Journal of Cardiovascular Pharmacology 1994;23(Suppl 4):S60‐S64.

DeQuattro 1997 {published data only}

DeQuattro V, Lee D, Messerli F. Efficacy of combination therapy with trandolapril and verapamil SR in primary hypertension: A 4 X 4 trial design. Clinical and Experimental Hypertension 1997;19(3):373‐87.
DeQuattro V, Lee D, and the Trandolapril Study Group. Fixed‐dose combination therapy with trandolapril and verapamil SR is effective in primary hypertension. American Journal of Hypertension 1997;10(7 Pt 2):138S‐145S.
Levine JH, Applegate WB. Trandolapril and verapamil slow release in the treatment of hypertension: A dose‐response assessment with the use of a multifactorial trial design. Current Therapeutic Research 1997;58(6):361‐74.

Drayer 1983 {published data only}

Drayer J, Weber MA. Monotherapy of essential hypertension with a converting‐enzyme inhibitor. Hypertension 1983;5(Suppl III):III108‐13.

Dupui 1993 {published data only}

Dupui P, Larrue V, Pavy‐Le Traon A, Allavoine T, Geraud G, Bes A. Effects of a captopril‐induced decrease of the arterial blood pressure on the cerebral blood flow of elderly subjects with moderate hypertension [Consequences d'une diminution de la pression sanguine arterielle induite par le captopril sur l'hemodynamique cerebrale du sujet age moderement hypertendu]. Circulation et metabolisme du cerveau 1993;10(3‐4):143‐56.
Larrue V, Dupui P, Pave‐Le Traon A, Allavoine T, Geraud G, Bes A. Cerebral blood flow changes induced by a chronic treatment with captopril in previously untreated elderly hypertensive subjects [Effets du captopril sur le debit sanguin cerebral du sujet age hypertendu]. Archives des Maladies du Coeur et des Vaisseaux 1994;87(8):997‐1000.

Fairhurst 1994 {published data only}

Fairhurst GJ. A multicentre multidose study of the efficacy and safety of spirapril in mild‐to‐moderate essential hypertension. Blood Pressure 1994;3(Suppl 2):77‐80.

Fernandez 1990 {published data only}

Fernandez PG, Bolli P, Lee C. The 24 h blood pressure responses of hypertensives to a once‐a‐day cilazapril regimen. Canadian Journal of Cardiology 1990;6(2):53‐8.
Fernandez PG, Bolli P, Lee C, Vasdev S. Cilazapril inhibits vascular responses to baroreflex‐stimulated sympathetic neural activity in hypertensive patients. Canadian Journal of Cardiology 1990;6(1):9‐14.

Fernandez 1994 {published data only}

Fernandez M, Madero R, Gonzalez D, Camacho P, Villalpando J, Arriaga J. Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients. Hypertension 1994;23(Suppl 1):I207‐10.

Ford 1993 {published data only}

Ford NF, Fulmor IE, Nichola PS, Alpin PG, Herron JM. Fosinopril monotherapy: Relationship between blood pressure reduction and time of administration. Clinical Cardiology 1993;16(4):324‐30.

Gerritsen 1998 {published data only}

Gerritsen TA, Bak AAA, Stolk RP, Jonker JJC, Grobbee DE. Effects of nitrendipine and enalapril on left ventricular mass in patients with non‐insulin‐dependent diabetes mellitus and hypertension. Journal of Hypertension 1998;16(5):689‐96.

Gomez 1989 {published data only}

Gomez HJ, Cirillo VJ, Sromosky JA, Otterbein ES, Shaw WC, Rush JE, Chrysant SG, Gradman AH, Leon AS, MacCarthy P, Nelson EB, Pool J, Vedin A. Lisinopril dose‐response relationship in essential hypertension. British Journal of Clinical Pharmacology 1989;28(4):415‐20.

Gradman 1995 {published data only}

Gradman AH, Arcuri KE, Goldberg AI, Ikeda LS, Nelson EB, Snavely DB, Sweet CS. A randomized, placebo‐controlled, double‐blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension. Hypertension 1995;25(6):1345‐50.

Gradman 1997 {published data only}

Gradman AH, Cutler NR, Davis PJ, Robbins JA, Weiss RJ, Wood BC. Combined enalapril and felodipine extended release (ER) for systemic hypertension. American Journal of Cardiology 1997;79(4):431‐5.

Guitard 1994 {published data only}

Guitard C, Alvisi V, Maibach E, Franck J, Cocco G, Boxho G, Mellein B, Waite R. Placebo‐controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension. Blood Pressure 1994;3(Suppl 2):81‐7.

Guitard 1997 {published data only}

Guitard C, Lohmann FW, Alfiero R, Ruina M, Alvisi V. Comparison of efficacy of spirapril and enalapril in control of mild‐to‐moderate hypertension. Cardiovascular Drugs and Therapy 1997;11(3):449‐57.

Guntzel 1991 {published data only}

Guntzel P, Kobrin I, Pasquier C, Zimlichman R, Viskoper JR. The effect of cilazapril, a new angiotensin converting enzyme inhibitor, on peak and trough blood pressure measurements in hypertensive patients. Journal of Cardiovascular Pharmacology 1991;17(1):8‐12.
Kobrin I, Guntzel P, Viskoper R, Paran E, Zimlichman R. Antihypertensive duration of action of cilazapril in patients with mild to moderate essential hypertension. Drugs 1991;41(Suppl. 1):31‐6.

Holwerda 1996 {published data only}

Holwerda NJ, Fogari R, Angeli P, Porcellati C, Hereng C, Oddou‐Stock P, Heath R, Bodin F. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril. Journal of Hypertension 1996;14(9):1147‐51.

Homuth 1993 {published data only}

Homuth V, Faulhaber H‐D, Loose U, Loffler K, Luft FC. Usefulness of piretanide plus ramipril for systemic hypertension: A multicenter trial. American Journal of Cardiology 1993;72(9):666‐71.

Kayanakis 1987 {published data only}

Kayanakis JG, Baulac L. Comparative study of once‐daily administration of captopril 50 mg, hydrochlorothiazide 25 mg and their combination in mild to moderate hypertension. British Journal of Clinical Pharmacology 1987;23(23 Suppl 1):89S‐92S.

Kobrin 1991 {published data only}

Kobrin I, Guntzel P, Viskoper R, Paran E, Zimlichman R. Antihypertensive duration of action of cilazapril in patients with mild to moderate essential hypertension. Drugs 1991;41(Suppl 1):31‐6.

Koch 1999 {published data only}

Koch B, Oparil S, Stimpel M. Co‐administration of an ACE‐inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women. Journal of Human Hypertension 1999;13(5):337‐42.

Kohlmann Jr 1999 {published data only}

Kohlmann Jr O, Jardim PCBV, Oigman W. Brazilian multicenter study on efficacy and tolerability of trandolapril in mild‐to‐moderate essential arterial hypertension: EMBATHE substudy with ambulatory blood pressure monitoring [Estudo multicentrico brasileiro de avaliacao da eficacia e tolerabilidade de trandolapril na hipertensao arterial essencial leve a moderada: EMBATHE subestudo com monitorizacao arterial de pressao arterial]. Arquivos Brasileiros de Cardiologia 1999;72(5):547‐52.

Kostis 1991 {published data only}

Kostis JB. Double‐blind study of ascending doses of ramipril in patients with mild to moderate hypertension. Advances in Therapy 1991;8(1):6‐17.
Schnaper HW. Dose‐response relationship of ramipril in patients with mild‐to‐moderate hypertension. Journal of Cardiovascular Pharmacology 1991;18(Suppl 2):S128‐S130.

Krum 1992 {published data only}

Krum H, Jackson B, Conway EL, Howes LG, Johnston CI, Louis WJ. Steady‐state pharmacokinetics and pharmacodynamics of cilazapril in the presence and absence of cyclopenthiazide. Journal of Cardiovascular Pharmacology 1992;20(3):451‐7.

Krum 1998 {published data only}

Krum H, Viskoper RJ, Lacourciere Y, Budde M, Charlon V. The effect of an endothelin‐receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. New England Journal of Medicine 1998;338(12):784‐90.

Kuppers 1997 {published data only}

Kuppers HE, Jager BA, Luszick JH, Grave MA, Hughes PR, Kaan EC. Placebo‐controlled comparison of the efficacy and tolerability of once‐daily moxonidine and enalapril in mild‐to‐moderate essential hypertension. Journal of Hypertension 1997;15:93‐7.

Kuschnir 1996 {published data only}

Kuschnir E, Acuna E, Sevilla D, Vasquez J, Bendersky M, Resk J, Glazer R. Treatment of patients with essential hypertension: Amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo. Clinical Therapeutics 1996;18(6):1213‐24.

Lacourciere 1994 {published data only}

Lacourciere Y, Leenen F, Rangno R, Spence JD, Lenis JH, Myers MG. Discrepancies between clinic and ambulatory blood pressure responses to cilazapril therapy. Canadian Journal of Cardiology 1994;10(6):605‐10.

Lerch 1999 {published data only}

Lerch M, Weidmann P, Ho MP, Gerber P, Eckenberger P, Kaemmereit A, Teuscher AU. Metabolic effects of temocapril in hypertensive patients with diabetes mellitus type 2. Journal of Cardiovascular Pharmacology 1999;33(4):527‐33.

Levine 1995 {published data only}

Levine JH, Ferdinand KC, Cargo P, Laine H, Lefkowitz M. Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension. American Journal of Hypertension 1995;8(5 Pt 1):494‐9.

Luccioni 1988 {published data only}

Luccioni R, Gass FR, Schwab C, Santoni JP, Perret L. Evaluation of the dose‐effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder. European Heart Journal 1988;9:1131‐6.

MacLean 1989 {published data only}

Maclean D. Quinapril: A double‐blind, placebo‐controlled trial in essential hypertension. Angiology 1989;40(4 Pt 2):370‐81.

Mancia 1992 {published data only}

Mancia G, De Cesaris R, Fogari R, Lattuada S, Montemurro G, Palomba C, Porcellati C, Ranieri G, Tettamanti F, Verdecchia P, Marelli C, Omboni S, Ravogli A, Zanchetti A. Evaluation of the antihypertensive effect of once‐a‐day trandolapril by 24‐hour ambulatory blood pressure monitoring. American Journal of Cardiology 1992;70(12):60D‐66D.
Ravogli A, Omboni S, De Cesaris R, Fogari R, Lattuada S, Montemurro G, Palombo C, Porcellati C, Ranieri G, Tettamanti F, Verdecchia P, Marelli C, Zanchetti A, Mancia G. Twenty‐four hour ambulatory blood pressure monitoring and antihypertensive treatment: Focus on ACE inhibitors. Journal of Cardiovascular Pharmacology 1994;23(Suppl 1):S15‐S19.

Mancia 1997 {published data only}

Mancia G, Agabiti‐Rosei E, Benetti G, Calcagnini G, Campa PP, Carretta R, Casati R, Coca A, De la Sierra A, Federighi G, Fogari R, Fontana S, Gomez B, Infelise V, Nami R, Pasotti C, Pirrelli A, Otero L, Vidal L. Effects of verapamil SR, trandolapril, and their fixed combination on 24‐h blood pressure: The Veratran Study. American Journal of Hypertension 1997;10(5 Pt 1):492‐9.

McCarron 1991 {published data only}

Burris JF. The effect of ramipril on ambulatory blood pressure: A multicenter trial. Journal of Cardiovascular Pharmacology 1991;18(Suppl 2):S131‐S133.
McCarron D. 24‐hour blood pressure profiles in hypertensive patients administered ramipril or placebo once daily: magnitude and duration of antihypertensive effects. Cardiology 1991;14(9):737‐42.

McFate‐Smith 1991 {published data only}

Gomez HJ, Glazer R, Mallows S, De Silva J. Benazepril in the treatment of older and elderly hypertensive patients. Benazepril: Profile of a new ACE inhibitor. Royal Society of Medicine Services International Congress and Symposium Series. London: Royal Society of Medicine Services Limited, 1990, issue 166:111‐21.
McFate Smith W, Gomez HJ. The use of benazepril in hypertensive patients age 55 and over. Clinical Cardiology 1991;14(Suppl IV):IV79‐82.

Messerli 1998 {published data only}

Messerli F, Frishman WH, Elliott WJ. Effects of verapamil and trandolapril in the treatment of hypertension. American Journal of Hypertension 1998;11(3 Pt 1):322‐7.

Moser 1991 {published data only}

Gomez HJ. Dose‐response studies with benazepril in mild to moderate hypertension. Clinical Cardiology 1991;14(Suppl IV):IV‐22‐7.
Moser M, Abraham PA, Bennett WM, Brachfeld N, Goodman RP, McKenney JM, Hollifield JW, Kirkendall WM, Lasseter KC, Leon AS, Lunn JA, Miller K, Morganroth J, Ruddy MC, Sambhi MP, Stein WJ, Weber MA, Williams RL, Zawada ET, DeSilva J, Gourley LA, Whalen JJ. The effects of benazepril, a new angiotensin‐converting enzyme inhibitor, in mild to moderate essential hypertension: A multicenter study. Clinical Pharmacology and Therapeutics 1991;49(3):322‐9.
Moser M, Whalen J, Gourley L, DeSilva J. Double‐blind comparison of benazepril, hydrochlorothiazide, and placebo in mild to moderate hypertension. American Journal of Hypertension 1989;2(5 Pt 2):44A.

Mroczek 1991 {published data only}

Mroczek WJ, Klein J, Burris JF. Dose‐finding study of cilazapril (Inhibace(TM)) in patients with uncomplicated essential hypertension. Clinical and Experimental Hypertension ‐ Theory and Practice 1991;13(8):1415‐32.

Mroczek 1996 {published data only}

Mroczek WJ, Stimpel M. A double‐blind evaluation of moexipril versus hydrochlorothiazide in hypertension. Advances in Therapy 1996;13(2):79‐87.

Muiesan 1987 {published data only}

Muiesan G, Agabiti‐Rosei E, Buoninconti R, Cagli V, Carotti A, Corea L, Innocenti P, Malerba M, Paciaroni E, Pirrelli A, Toso M, Botta G. Antihypertensive efficacy and tolerability of captopril in the elderly: Comparison with hydrochlorothiazide and placebo in multicentre, double‐blind study. Journal of Hypertension 1987;5(Suppl 5):S599‐S602.

Myers 1996 {published data only}

Myers MG. A dose‐response study of perindopril in hypertension: Effects on blood pressure 6 and 24 h after dosing. Canadian Journal of Cardiology 1996;12(11):1191‐6.

New 2000 {published data only}

New JP, Bilous RW, Walker M. Insulin sensitivity in hypertensive type 2 diabetic patients after 1 and 19 days' treatment with trandolapril. Diabetic Medicine 2000;17(2):134‐40.

Oparil 1999 {published data only}

Oparil S. Eprosartan versus enalapril in hypertensive patients with angiotensin‐converting enzyme inhibitor‐induced cough. Current Therapeutic Research 1999;60(1):1‐4.

Overlack 1994 {published data only}

Bonner G, Lederle RM, Scholze J, Stumpe KO. Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant therapy. Arzneimittel‐Forschung 1993;43(8):852‐5.
Middeke M, Krone W. Effects of perindopril on serum lipids in hypertensive patients with hyperlipidemia. Journal of Cardiovascular Pharmacology 1994;23(4):629‐31.
Overlack A, Adamczak M, Bachmann W, Bonner G, Bretzel RG, Derichs R, Krone W, Lederle RM, Reimann HJ, Zschiedrich H, Stumpe KO. ACE‐inhibition with perindopril in essential hypertensive patients with concomitant diseases. American Journal of Medicine 1994;97(2):126‐34.
Overlack A, Kronig B, Stumpe KO. Clinical and functional course of COPD in hypertensive patients with concomitant chronic bronchitis and emphysema during treatment with an ACE inhibitor, perindopril. Journal of Drug Development 1993;6(1):5‐9.
Stumpe KO, Overlack A. A new trial of the efficacy, tolerability, and safety of angiotensin‐converting enzyme inhibition in mild systemic hypertension with concomitant diseases and therapies. American Journal of Cardiology 1993;71(17):32E‐37E.
Stumpe KO, Overlack A. Angiotensin‐converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study. The American Journal of Medicine 1992;92(4B):98S‐101S.

Persson 1996 {published data only}

Persson B, Stimpel M. Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients. European Journal of Clinical Pharmacology 1996;50:259‐64.

Pittrow 1997 {published data only}

Pittrow DB, Antlsperger A, Welzel D, Wambach G, Schardt W, Weldinger G. Evaluation of the efficacy and tolerability of a low‐dose combination of isradipine and spirapril in the first‐line treatment of mild to moderate essential hypertension. Cardiovascular Drugs and Therapy 1997;11(5):619‐27.

Pizarro 1996 {published data only}

Pizarro M, Lima J, Domingues J, Gouveia AC, Monteiro A, Carrageta M, de Freitas AF. Antihypertensive effect of fosinopril in mild hypertension [Efeito anti‐hipertensor do fosinopril na hipertensao arterial ligeira]. Revista Portuguesa de Cardiologia 1996;15(6):495‐7,460.

Poirier 1991 {published data only}

Lacourciere Y, Poirier L, Pyzyk M. 2.5 and 5 mg cilazapril once daily compared with placebo in hypertension: A comparative out‐patient study of 24‐hour blood pressure monitoring [2,5 und 5 mg cilazapril einmal taglich verglichen mit plazebo bei hypertonie: Eine vergleichsstudie mit ambulantem 24‐studen‐monitoring]. Cardiology 1993;82(Suppl 2):78‐82.
Poirier L, Pyzyk M, Provencher P, Lacourciere Y. Comparative effects of 2.5 and 5 mg cilazapril versus placebo on daily blood pressure load. American Journal of Hypertension 1991;4(11):913‐5.

Pool 1990 {published data only}

Pool JL. Antihypertensive effect of fosinopril, a new angiotensin converting enzyme inhibitor: Findings of the fosinopril study group II. Clinical Therapeutics 1990;12(6):520‐33.

Pool 1997 {published data only}

Pool JL, Cushman WC, Saini RK, Nwachuku CE, Battikha JP. Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension. American Journal of Hypertension 1997;10(1):117‐23.

Pool 2001 {published data only}

Pool J, Kaihlanen P, Lewis G, Ginsberg D, Oparil S, Glazer R, Messerli FH. Once‐daily treatment of patients with hypertension: a placebo‐controlled study of amlodipine and benazepril vs amlodipine or benazepril alone. Journal of Human Hypertension 2001;15(7):495‐8.

Pordy 1994 {published data only}

Pordy RC. Cilazapril plus hydrochlorothiazide: Improved efficacy without reduced safety in mild to moderate hypertension. Cardiology 1994;85(5):311‐22.

Prager 1994 {published data only}

Prager G, Klein P, Schmitt M, Prager R. Antihypertensive efficacy of cilazapril 2.5 and 5.0 mg once‐daily versus placebo on office blood pressure and 24‐hour blood pressure profile. Journal of Cardiovascular Pharmacology 1994;24(Suppl 3):S93‐9.

Prichard 2002 {published data only}

Prichard BN, Jager BA, Luszick JH, Kuster LJ, Verboom CN, Hughes PR, Sauermann W, Kuppers HE. Placebo‐controlled comparison of the efficacy and tolerability of once‐daily moxonidine and enalapril in mild to moderate essential hypertension. Blood Pressure 2002;11(3):166‐72.

Reimann 1995 {published data only}

Reimann HJ, Muller M, Trinczek‐Gartner H, Kirchhoff R, Kirchhoff G. ACE inhibition in hypertensive patients with concomitant NSAID therapy [ACE‐hemmung bei patienten mit hypertonie und gleichzeitiger NSAR‐therapie]. Munchener Medizinische Wochenschrift 1995;137(12):187‐91.

Roca‐Cusachs 2001 {published data only}

Roca‐Cusachs A, Torres F, Horas M, Rios J, Calvo G, Delgadillo J, Teran M. Nitrendipine and enalapril combination therapy in mild to moderate hypertension: Assessment of dose‐response relationship by a clinical trial of factorial design. Journal of Cardiovascular Pharmacology 2001;38(6):840‐9.

Sassano 1984 {published data only}

Sassano P, Chatellier G, Alhenc‐Gelas F, Corvol P, Menard J. Antihypertensive effect of enalapril as first‐step treatment of mild and moderate uncomplicated essential hypertension. American Journal of Medicine 1984;77(2A):18‐22.

Saynavalammi 1988 {published data only}

Saynavalammi P, Porsti I, Porsti P, Nurmi AK, Seppala E, Manninen V, Vapaatalo H. Effects of the converting enzyme inhibitor quinapril (CI‐906) on blood pressure, renin‐angiotensin system, and prostanoids in essential hypertension. Journal of Cardiovascular Pharmacology 1988;12(1):88‐93.

Schoenberger 1986 {published data only}

Schoenberger JA, Wilson DJ. Once‐daily treatment of essential hypertension with captopril. Journal of Clinical Hypertension 1986;2(4):379‐87.

Scholze 1998 {published data only}

Scholze J, Zilles P, Compagnone D. Verapamil SR and trandolapril combination therapy in hypertension ‐ a clinical trial of factorial design. British Journal of Clinical Pharmacology 1998;45(5):491‐5.

Scholze 1999 {published data only}

Scholze J, Bauer B, Massaro J. Antihypertensive profiles with ascending dose combinations of ramipril and felodipine ER. Clinical and Experimental Hypertension 1999;21(8):1447‐62.

Simon 1983 {published data only}

Morioka S, Simon G, Cohn JN. Cardiac and hormonal effects of enalapril in hypertension. Clinical Pharmacology and Therapeutics 1983;34(5):583‐9.
Simon G, Morioka S, Snyder DK, Cohn JN. Increased renal plasma flow in long‐term enalapril treatment of hypertension. Clinical Pharmacology and Therapeutics 1983;34(4):459‐65.

Smith 1998 {published data only}

Smith DHG, Neutel JM, Morgenstern P. Once‐daily telmisartan compared with enalapril in the treatment of hypertension. Advances in Therapy 1998;15(4):229‐40.

Smith 2000 {published data only}

Smith DHG, Matzek KM, Kempthorne‐Rawson J. Dose response and safety of telmisartan in patients with mild to moderate hypertension. Journal of Clinical Pharmacology 2000;40(12 Pt 1):1380‐90.

Trevisan 1995 {published data only}

Trevisan R, Tiengo A. Effect of low‐dose ramipril on microalbuminuria in normotensive or mild hypertensive non‐insulin‐dependent diabetic patients. American Journal of Hypertension 1995;8(9):876‐83.

Uusitupa 1996 {published data only}

Uusitupa M, Korhonen M, Litmanen, Niskanen L, Vaisanen S, Rauramaa R. Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure. Journal of Human Hypertension 1996;10(5):319‐26.

VA Study Group 1984 {published data only}

Veterans Administration Cooperation Study Group on Antihypertensive Agents. Low‐dose captopril for the treatment of mild to moderate hypertension. Archives of Internal Medicine 1984;144(10):1947‐53.
Veterans Administration Cooperative Study Group on Antihypertensive Agents. Racial differences in response to low‐dose captopril are abolished by the addition of hydrochlorothiazide. British Journal of Clinical Pharmacology 1982;14(Suppl 2):97S‐101S.

Vandenburg 1994 {published data only}

Vandenburg MJ, MacKay EM, Dews I, Pullan T, Brugier S. Dose finding studies with imidapril ‐ a new ACE inhibitor. British Journal of Clinical Pharmacology 1994;37(3):265‐72.

Vaur 1998 {published data only}

Vaur L, Dubroca I, Dutrey‐Dupagne C, Genes N, Chatellier G, Bouvier‐d'Yvoire M, Elkik F, Menard J. Superiority of home blood pressure measurements over office measurements for testing antihypertensive drugs. Blood Pressure Monitoring 1998;3(2):107‐14.

Villamil 1987 {published data only}

Villamil AS, Cairns V, Witte PU, Bertolasi CA. A double‐blind study to compare the efficacy, tolerance and safety of two doses of the angiotensin converting enzyme inhibitor ramipril with placebo. American Journal of Cardiology 1987;59(10):110D‐14D.

Waeber 1999 {published data only}

Waeber B, Detry JM, Dahlof B, Puig JG, Gundersen T, Hosie J, Januszewicz W, Lindstrom CJ, Magometschnigg D, Safar M, Tanser P, Toutouzas P. Felodipine‐metoprolol combination tablet: A valuable option to initiate antihypertensive therapy?. American Journal of Hypertension 1999;12(9 Pt 1):915‐20.

Weinberger 1990 {published data only}

Gomez HJ. Dose‐response studies with benazepril in mild to moderate hypertension. Clinical Cardiology 1991;14(8 Suppl IV):IV22‐7.
Weinberger MH, Black HR, Lasseter KC, Lewis GP, MacLeod CM, Pascual AV, Zager PG, DeSilva J, Gourley LA, Bennett DA, Whalen JJ. Diurnal blood pressure in patients with mild‐to‐moderate hypertension treated with once‐daily benazepril hydrochloride. Clinical Pharmacology and Therapeutics 1990;47(5):608‐17.

Weir 1995 {published data only}

Weir MR, Gray JM, Paster R, Saunders E. Differing mechanisms of action of angiotensin‐converting enzyme inhibition in black and white hypertensive patients. Hypertension 1995;26(1):124‐30.
Weir MR, Saunders E. Renin status does not predict the anti‐hypertensive response to angiotensin‐converting enzyme inhibition in African‐Americans. Journal of Human Hypertension 1998;12(3):189‐94.

Whalen 1989 {published data only}

Gomez HJ. Dose‐response studies with benazepril in mild to moderate hypertension. Clinical Cardiology 1991;14(8 Suppl IV):IV22‐7.
Whalen J, Skalky C, DeSilva J, Weber M. Peak and trough effects of 3 once daily dose levels of benazepril in mild‐moderate hypertension. American Journal of Hypertension 1989;2(5 Pt 2):45A.

Whelton 1992 {published data only}

Whelton A, Dunne Jr B, Glazer N, Kostis JB, Miller WE, Rector DJ, Tresznewsky ON. Twenty‐four hour blood pressure effect of once‐daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension. Journal of Human Hypertension 1992;6(4):325‐31.

White 1988 {published data only}

White WB, McCabe EJ, Hager WD, Schulman P. The effects of the long‐acting angiotensin‐converting enzyme inhibitor cilazapril on casual, exercise, and ambulatory blood pressure. Clinical Pharmacology and Therapeutics 1988;44(2):173‐8.

White 1995 {published data only}

White WB, Whelton A, Fox A, Stimpel M, Kaihlanen PM. Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring. Journal of Clinical Pharmacology 1995;35(3):233‐8.

White 2002 {published data only}

White WB, Sica DA, Calhoun D, Mansoor GA, Anders RJ. Preventing increases in early‐morning blood pressure, heart rate, and the rate‐pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising. American Journal of Hypertension 2002;144(4):657‐65.

Yebes 1993 {published data only}

Yebes RB. A placebo‐controlled double blind study to evaluate the efficacy of once daily quinapril in patients with mild to moderate hypertension. Philippine Journal of Internal Medicine 1993;31(6):317‐26.

Yodfat 1993 {published data only}

Yodfat Y, Zimilchman R. Dose‐finding and dose justification of once‐daily cilazapril in combination with hydrochlorothiazide in non‐obese patients with mild‐to‐moderate essential hypertension. Journal of Drug Development 1993;6(3):117‐21.

Zamboulis 1996 {published data only}

Zamboulis C, Karagiannis A, Gotzamani‐Psarrakou A, Deligianni K, Spyridonidis T, Fragos S, Psarrakos K. Effects of fosinopril on renal function in patients with mild to moderate essential hypertension. Clinical Drug Investigation 1996;12(5):251‐8.

References to studies excluded from this review

Ir a:

Bainbridge 1993 {published data only}

Bainbridge AD, MacFadyen RJ, Stark S, Lees KR, Reid JL. The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension. British Journal of Clinical Pharmacology 1993;36(4):323‐30.

Bakris 2002 {published data only}

Bakris G, Sica D, Ram V, Fagan T, Vaitkus PT, Anders RJ. A comparative trial of controlled‐onset, extended‐release verapamil, enalapril, and losartan on blood pressure and heart rate changes. American Journal of Hypertension 2002;15(1 I):53‐7.

Beaulieu 1993 {published data only}

Beaulieu M, Lacourciere Y, Cleroux J. Unchanged neurogenic vasoconstrictor response after exercise during angiotensin converting enzyme inhibition with fosinopril. American Journal of Hypertension 1994;7(8):763‐6.
Beaulieu M, Nadeau A, Lacourciere Y, Cleroux J. Post‐exercise reduction in blood pressure in hypertensive subjects: Effects of angiotensin converting enzyme inhibition. British Journal of Clinical Pharmacology 1993;36(4):331‐8.

Bergstrand 1985 {published data only}

Bergstrand R, Herlitz H, Johansson S, Berglund G, Vedin A, Wilhelmsson C, et al. Effective dose range of enalapril in mild to moderate essential hypertension. British Journal of Clinical Pharmacology 1985;19(5):605‐11.

Bohlen 1996 {published data only}

Bohlen L, Bienz R, Doser M, Papiri M, Shaw S, Riesen W, et al. Metabolic neutrality of perindopril: focus on insulin sensitivity in overweight patients with essential hypertension. Journal of Cardiovascular Pharmacology 1996;27(6):770‐6.

Canter 1994 {published data only}

Canter D, Frank GJ, Knapp LE, Phelps M, Quade M, Texter M. Quinapril and hydrochlorothiazide combination for control of hypertension: assessment by factorial design. Quinapril Investigator Group [see comments]. Journal of Human Hypertension 1994;8(3):155‐62.

Canter 1994a {published data only}

Canter DA, Texter MJ, McLain RW. Ambulatory blood pressure monitoring can play an integral role in patient selection, dosage adjustment and efficacy assessment in clinical trials of antihypertensive agents. Journal of Hypertension ‐ Supplement 1994;12(7):S33‐8.

Cleroux 1994 {published data only}

Cleroux J, Beaulieu M, Kouame N, Lacourciere Y. Comparative effects of quinapril, atenolol, and verapamil on blood pressure and forearm hemodynamics during handgrip exercise. American Journal of Hypertension 1994;7(6):566‐70.

Cuspidi 1997 {published data only}

Cuspidi C, Lonati L, Sampieri L, Leonetti G, Muiesan ML, Agabiti‐Rosei E, et al. Lack of effect of short‐term lisinopril administration on left ventricular filling dynamics in hypertensive patients with diastolic dysfunction. Blood Pressure 1997;6(5):307‐12.

Duprez 1986 {published data only}

Duprez D, Clement DL. Vasodilator effects of enalapril in patients with arterial hypertension. Acta Cardiologica 1986;41(5):359‐64.

Fagard 2001 {published data only}

Fagard R, Lijnen P, Pardaens K, Thijs L, Vinck W. A randomised, placebo‐controlled, double‐blind, crossover study of losartan and enalapril in patients with essential hypertension. Journal of Human Hypertension 2001;15(3):161‐7.

Gall 1992 {published data only}

Gall MA, Rossing P, Skott P, Hommel E, Mathiesen ER, Gerdes LU, et al. Placebo‐controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non‐insulin‐dependent diabetic patients with primary hypertension. American Journal of Hypertension 1992;5(5 Pt 1):257‐65.

Gans 1993 {published data only}

Gans RO, Stehouwer CD, Bilo HJ, Goggin T, Kraaij CJ, Donker AJ, et al. Effect of cilazapril on glucose tolerance and lipid profile in hypertensive patients with non‐insulin‐dependent diabetes mellitus. Netherlands Journal of Medicine 1993;43(3‐4):163‐73.

Gleerup 1996 {published data only}

Gleerup G, Petersen JR, Mehlsen J, Winther K. Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension. Angiology 1996;47(10):951‐5.

Guitard 1994a {published data only}

Guitard C, Alvisi V, Maibach E, Franck J, Cocco G, Boxho G, et al. Placebo‐controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension. Blood Pressure 1994;Supplement. 2:81‐7.

Gupta 1990 {published data only}

Gupta RK, Kjeldsen SE, Krause L, Kneisley J, Posvar E, Weder AB, et al. Hemodynamic effects of quinapril, a novel angiotensin‐converting enzyme inhibitor. Clinical Pharmacology & Therapeutics 1990;48(1):41‐9.
Gupta RK, Kjeldsen SE, Motley E, Weder AB, Zweifler AJ, Julius S. Platelet function during antihypertensive treatment with quinapril, a novel angiotensin converting enzyme inhibitor. Journal of Cardiovascular Pharmacology 1991;17(1):13‐9.

Homuth 1993a {published data only}

Homuth V, Faulhaber HD, Loose U, Loffler K, Luft FC. Usefulness of piretanide plus ramipril for systemic hypertension: a multicenter trial. American Journal of Cardiology 1993;72(9):666‐71.

Hu 1999 {published data only}

Hu Y, Zhu J. Quality of life of patients with mild hypertension treated with captopril: A randomized double‐blind placebo‐controlled clinical trial. Chinese Medical Journal 1999;112(4):302‐7.

Kahan 1999 {published data only}

Kahan T, Eliasson K. The influence of long‐term ACE inhibitor treatment on circulatory responses to stress in human hypertension. American Journal of Hypertension 1999;12(12 I):1188‐94.

Karlberg 1987 {published data only}

Karlberg BE, Lindstrom T, Rosenqvist U, Ohman KP. Efficacy, tolerance and hormonal effects of a new oral angiotensin converting enzyme inhibitor, ramipril (HOE 498), in mild to moderate primary hypertension. American Journal of Cardiology 1987;59(10):104D‐9D.

Kjeldsen 1992 {published data only}

Kjeldsen SE, Gupta RK, Krause L, Weder AB, Julius S. Does blood pressure reduction necessarily compromise cardiac function or renal hemodynamics? Effects of the angiotensin‐converting enzyme inhibitor quinapril. American Heart Journal 1992;123(5):1433‐8.

Lacourciere 1999 {published data only}

Lacourciere Y, Bittar N, Blanchard E, Kilpatrick FW, Schumacher D, Chappel C, et al. The incidence of cough: A comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. International Journal of Clinical Practice 1999;53(2):99‐103.

Lavezzaro 1990 {published data only}

Lavezzaro G, Ladetto PE, Valente M, Stramignoni D, Zanna C, Assogna G, et al. Ketanserin and captopril interaction in the treatment of essential hypertensives. Cardiovascular Drugs & Therapy 1990;4(SUPPL. 1):119‐22.

Leonetti 1991 {published data only}

Leonetti G, Mazzola C, Pasotti C, Angioni L, Vaccarella A, Capra A, et al. Treatment of hypertension in the elderly: Effects on blood pressure, heart rate, and physical fitness. American Journal of Medicine 1991;90(SUPPL.3A):12S‐3S.

Littler 1990 {published data only}

Littler WA, West JW. Twenty‐four hour action of ACE inhibitors. Journal of Human Hypertension 1990;4(SUPPL. 4):13‐6.

Louis 1992 {published data only}

Louis WJ, Workman BS, Conway EL, Worland P, Rowley K, Drummer O, et al. Single‐dose and steady‐state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects. Journal of Cardiovascular Pharmacology 1992;20(3):505‐11.

Miyajima 1999 {published data only}

Miyajima E, Shigemasa T, Yamada Y, Tochikubo O, Ishii M. Angiotensin II blunts, while an angiotensin‐converting enzyme inhibitor augments, reflex sympathetic inhibition in humans. Clinical & Experimental Pharmacology & Physiology 1999;26(10):797‐802.

Morgan 2001 {published data only}

Morgan TO, Anderson AI, MacInnis RJ. ACE inhibitors, beta‐blockers, calcium blockers, and diuretics for the control of systolic hypertension. American Journal of Hypertension 2001;14(3):241‐7.

Petersen 1996 {published data only}

Petersen JR, Drabaek H, Gleerup G, Mehlsen J, Petersen LJ, Winther K. ACE inhibition with spirapril improves diastolic function at rest independent of vasodilation during treatment with spirapril in mild to moderate hypertension. Angiology 1996;47(3):233‐40.

Petrie 2000 {published data only}

Petrie JR, Morris AD, Ueda S, Small M, Donnelly R, Connell JM, et al. Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double‐blind, placebo‐controlled crossover trial. Journal of Clinical Endocrinology & Metabolism 2000;85(5):1882‐9.

Petrov 2001 {published data only}

Petrov VV, Fagard RH, Lijnen PJ. T‐lymphocyte and plasma angiotensin‐converting enzyme activity during enalapril and losartan administration in humans. Journal of Cardiovascular Pharmacology 2001;38(4):578‐83.

Plouin 1991 {published data only}

Plouin PF, Battaglia C, Alhenc‐Gelas F, Corvol P. Are angiotensin converting enzyme inhibition and aldosterone antagonism equivalent in hypertensive patients over fifty?. American Journal of Hypertension 1991;4(4 Pt 1):356‐62.

Pritchard 1996 {published data only}

Pritchard G, Lyons D, Webster J, Petrie JC, MacDonald TM. Do trandolapril and indomethacin influence renal function and renal functional reserve in hypertensive patients?. British Journal of Clinical Pharmacology 1997;44(2):145‐9.
Pritchard G, Lyons D, Webster J, Petrie JC, MacDonald TM. Indomethacin does not attenuate the hypotensive effect of trandolapril. Journal of Human Hypertension 1996;10(11):763‐7.

Reisin 1997 {published data only}

Reisin E, Weir MR, Falkner B, Hutchinson HG, Anzalone DA, Tuck ML. Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo‐controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group. Hypertension 1997;30(1 Pt 1):140‐5.

Salvetti 1987 {published data only}

Salvetti A, Innocenti PF, Iardella M, Pambianco F, Saba GC, Rossetti M, et al. Captopril and nifedipine interactions in the treatment of essential hypertensives: a crossover study. Journal of Hypertension ‐ Supplement 1987;5(4):S139‐42.

Salvetti 1988 {published data only}

Salvetti A, Circo A, Raciti S, Gulizia M, Cardillo R, Miceli S, et al. Captopril at 50 mg as well as at 100 mg once a day reduces blood pressure for up to 24 h: a double‐blind randomized crossover study in mild to moderate hypertensives. Journal of Hypertension ‐ Supplement 1988;6(4):S666‐8.

Salvetti 1989 {published data only}

Salvetti A, Arzilli F. Chronic dose‐response curve of enalapril in essential hypertensives. An Italian multicenter study. American Journal of Hypertension 1989;2(5 Pt 1):352‐4.

Samuelsson 1992 {published data only}

Samuelsson O, Hedner T, Ljungman S, Herlitz H, Widgren B, Pennert K. A comparative study of lisinopril and atenolol on low degree urinary albumin excretion, renal function and haemodynamics in uncomplicated, primary hypertension. European Journal of Clinical Pharmacology 1992;43(5):469‐75.

Sassano 1984a {published data only}

Sassano P, Chatellier G, Amiot AM, Alhenc‐Gelas F, Corvol P, Menard J. A double‐blind randomized evaluation of converting enzyme inhibition as the first‐step treatment of mild to moderate hypertension. Journal of Hypertension ‐ Supplement 1984;2(2):S75‐80.

Scholze 1993 {published data only}

Scholze J, Breitstadt A, Cairns V, Bauer B, Bender N, Priestley C, et al. Short report: ramipril and hydrochlorothiazide combination therapy in hypertension: a clinical trial of factorial design. The East Germany Collaborative Trial Group. Journal of Hypertension 1993;11(2):217‐21.

Thurig 1995 {published data only}

Thurig C, Bohlen L, Schneider M, de Courten M, Shaw SG, Riesen W, et al. Lisinopril is neutral to insulin sensitivity and serum lipoproteins in essential hypertensive patients. European Journal of Clinical Pharmacology 1995;49(1‐2):21‐6.

Tomei 1992 {published data only}

Tomei R, Rossi L, Carbonieri E, Franceschini L, Molon G, Zardini P. Antihypertensive effect of lisinopril assessed by 24‐hour ambulatory monitoring: a double‐blind, placebo‐controlled, cross‐over study. Journal of Cardiovascular Pharmacology 1992;19(6):911‐4.

Wiggam 1998 {published data only}

Wiggam MI, Hunter SJ, Atkinson AB, Ennis CN, Henry JS, Browne JN, et al. Captopril does not improve insulin action in essential hypertension: a double‐blind placebo‐controlled study. Journal of Hypertension 1998;16(11):1651‐7.

Wilkins 1983 {published data only}

Wilkins LH, Dustan HP, Walker JF, Oparil S. Enalapril in low‐renin essential hypertension. Clinical Pharmacology & Therapeutics 1983;34(3):297‐302.

Wing 1987 {published data only}

Wing LM, Chalmers JP, West MJ, Bune AJ, Russell AE, Elliott JM, et al. Treatment of hypertension with enalapril and hydrochlorothiazide or enalapril and atenolol: contrasts in hypotensive interactions. Journal of Hypertension ‐ Supplement 1987;5(5):S603‐6.

Wing 1988 {published data only}

Wing LM, Chalmers JP, West MJ, Russell AE, Morris MJ, Cain MD, et al. Enalapril and atenolol in essential hypertension: attenuation of hypotensive effects in combination. Clinical & Experimental Hypertension ‐ Part A, Theory & Practice 1988;10(1):119‐33.

Youssef 1993 {published data only}

Youssef S, Osman L, Sabbour MS. Serum lipoprotein profile under different antihypertensive therapy. Cardiovascular Risk Factors 1993;3(2):107‐11.

Zanchetti 2001 {published data only}

Zanchetti A, Omboni S. Comparison of candesartan versus enalapril in essential hypertension. Italian Candesartan Study Group. American Journal of Hypertension 2001;14(2):129‐34.

Additional references

Ir a:

Bucher 1997

Bucher HC, Guyatt GH, Griffith LE, Walter D. The results of direct and indirect treatment comparisons in meta‐analysis of randomized controlled trials. Journal of Clinical Epidemiology 1997;50(6):683‐91.

Cochrane Handbook

Sterne JAC, Egger M, Moher D (editors). Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Intervention. The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org, Version 5.0.0 (updated February 2008).

Heran 2002

Heran BS, Jauca CD, Wright JM. Development of an optimal search strategy for finding trials demonstrating ACE inhibitor blood pressure lowering efficacy. 10th International Cochran Colloquium, Stavenger, Norway2002.

Jadad 1996

88.Jadad AR, Moore RA, Carrol D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary?. Controlled Clinical Trials 1996;17:1‐12.

Song 2003

Song F, Altman DG, Glenny AM Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: emperical evidence from published meta‐analyses. British Medical Journal 2003;326:472‐76.

WHO‐ICTRP

World Health Organization. International Clinical Trials Registry Platform (ICTRP). Available from: http://www.who.int/ictrp/en 2006 [cited 2008 Feb 29].

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Applegate 1996

Methods

7‐day washout period; 4‐week single‐blind placebo baseline phase; inclusion criteria= average sitting DBP 95‐115 mm Hg of week 2 and 4 of baseline phase recordings; 6‐week double‐blind treatment

Participants

Enalapril 5 mg: n=56(38 males,18 females); mean age=52.5(11.2) years; baseline SBP=152.8(17.3) mm Hg, DBP=100.5(5.2) mm Hg, HR=77.4(9.2) bpm;
Placebo: n=58(39 males,19 females); mean age=54.2(10.2) years; baseline SBP=152.5(13.0) mm Hg, DBP=100.4(4.8) mm Hg, HR=76.8(10.0) bpm

Interventions

Enalapril 5 mg once daily;
Placebo;
administered in the morning (between 7:30 AM and 10:00 AM)

Outcomes

Adjusted mean change from baseline in SBP/DBP using mercury sphygmomanometer;
Trough sitting SBP/DBP using mercury sphygmomanometer;
HR;
WDAE

Notes

Adjusted BP change reported, SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; used endpoint BP and SD data to calculate change in BP instead of entering adjusted BP change data; BP data from Table II, p. 53; Jadad score=4; funding source= Merck

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Belz 1986

Methods

4‐week placebo washout; inclusion criteria= DBP 95‐114 mm Hg; 4‐week double‐blind treatment

Participants

Cilazapril 1.25 mg: n=8(4 males,4 females); mean age=47.8(7.1) years; baseline sitting SBP=154.1(10.6) mm Hg, DBP=103.6(6.7) mm Hg;
Cilazapril 2.5 mg: n=6(3 males,3 females); mean age=47.2(9.1) years; baseline sitting SBP=149.8(13.2) mm Hg, DBP=100.2(4.4) mm Hg;
Cilazapril 5 mg: n=6(2 males,4 females); mean age=51.5(9.1) years; baseline sitting SBP=162.2(24.0) mm Hg, DBP=104.3(5.5) mm Hg;
Placebo: n=7(3 males,4 females); mean age=52.7(9.6) years; baseline sitting SBP=148.3(17.3) mm Hg, DBP=98.3(4.9) mm Hg

Interventions

Cilazapril 1.25 mg once daily;
Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo;
administered in the morning at approximately 7 AM

Outcomes

Peak sitting SBP/DBP

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Table 2, p. 526; lying and standing BP data also available; Jadad score=2; funding source= Hoffmann‐La Roche AG

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Black 1997

Methods

2‐ to 4‐week placebo run‐in; inclusion criteria= sitting DBP 95‐115 mm Hg after run‐in; 12‐week total double‐blind treatment, 4‐week double‐blind treatment at initial fixed dose, non‐responders were up‐titrated after 4 weeks

Participants

Lisinopril 10 mg: n=187(112 males,75 females); mean age=53.9(10.7) years; baseline sitting SBP=153.9(14.9) mm Hg, DBP=101.0(4.5) mm Hg;
Placebo: n=183(113 males,70 females); mean age=54.0(11.8) years; baseline sitting SBP=154.1(14.4) mm Hg, DBP=101.0(4.4) mm Hg

Interventions

Lisinopril 10 mg once daily;
Placebo;
administered at approximately 8 AM

Outcomes

Least mean square change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer

Notes

Used week 4 BP data only; BP change reported, SD of change not reported, endpoint BP and SD not reported; imputed SBP SD of change from baseline SBP SD of change, imputed overall trial mean DBP SD of change; SBP data from Figure 1, p. 487, DBP data from text, p. 485; Jadad score=2; funding source= Ciba‐Geigy

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Boeijinga 1993

Methods

Inclusion criteria= sitting DBP 90‐105 mm Hg before start of study; 3‐week double‐blind treatment

Participants

Cilazapril 2.5 mg: n=14(11 males,3 females); mean age=63.7(4.2) years; baseline SBP=139 mm Hg, DBP=92 mm Hg;
Placebo: n=12(10 males,2 females); mean age=63.3(7.8) years; baseline SBP=135 mm Hg, DBP=92 mm Hg

Interventions

Cilazapril 2.5 mg once daily;
Placebo;
administered in the morning before breakfast

Outcomes

Peak (2‐3 h after dosing) supine SBP/DBP using mercury sphygmomanometer;
Peak (2‐3 h after dosing) HR;
WDAE

Notes

Used DBP only since patients did not have SBP >/= 140 mm Hg at baseline; BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from text, p. 446; Jadad score=3; funding source= Hoffman‐La Roche Ltd.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Brown 1990

Methods

2‐week single‐blind placebo run‐in; inclusion criteria= supine DBP 95‐115 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

All patients: n=40(19 males,21 females); mean age=58 years; baseline upright SBP=154(15) mm Hg, DBP=102(7) mm Hg

Interventions

Perindopril 4 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough erect SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SEM of change reported, endpoint BP and SD not reported; calculated SD of change from N and SEM of change; BP data from Table 2, p. 329; Jadad score=4; funding source= Servier

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Carlsen 1995

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= mean pre‐dose sitting DBP 100‐115 mm Hg after 3 and 4 weeks of run‐in, mean baseline DBP >/= 100 mm Hg at hourly measurements 21‐24 h post‐placebo and also during whole BP profile (i.e. hourly measurements 1‐8 h and 21‐24 h post‐dose); 8‐week double‐blind treatment

Participants

Cilazapril 1 mg: n=42(26 males,16 females); mean age=53 years; baseline sitting BP not reported;
Cilazapril 2.5 mg: n=42(28 males,14 females); mean age=52 years; baseline sitting BP not reported;
Cilazapril 5 mg: n=42(27 males,15 females); mean age=48 years; baseline sitting BP not reported;
Placebo: n=43(22 males,21 females); mean age=56 years; baseline sitting BP not reported

Interventions

Cilazapril 1 mg once daily;
Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo;
taken at approximately 12 noon before meal

Outcomes

Mean change from baseline in trough sitting DBP using mercury sphygmomanometer

Notes

SBP change not reported; DBP change and SE of change reported, endpoint DBP and SD not reported; calculated DBP SD of change from N and SE of change; BP data from text, p. 224; Jadad score=2; funding source= Roche Ltd.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Chan 1997

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg at last 2 visits of run‐in; 12‐week double‐blind treatment

Participants

Lisinopril 10 mg: n=26(18 males,8 females); mean age=70.5 years; baseline sitting SBP=163.8(13.0) mm Hg, DBP=104.9(5.0) mm Hg, HR=62.5 bpm;
Placebo: n=27(15 males,12 females); mean age=73.4 years; baseline sitting SBP=167.9(14.8) mm Hg, DBP=105.5(5.4) mm Hg, HR=61.9 bpm

Interventions

Lisinopril 10 mg once daily;
Placebo;
taken between 8 AM and 10 AM

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change reported, endpoint BP and SD reported; SD of change values are too low; imputed endpoint SBP SD for SBP SD of change; imputed overall trial mean DBP SD of change; SBP data from Table 2, p. 745; DBP data from Table 3, p. 746; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Chrysant 1993

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= supine DBP 95‐114 mm Hg after run‐in; 16‐week double‐blind treatment, forced‐titration of dose by 4 mg every 4 weeks to maximum 16 mg daily

Participants

Perindopril 4‐16 mg once daily: n=117(65 males,52 females); mean age=55(10) years; baseline upright SBP=154(15) mm Hg, DBP=102(7) mm Hg; baseline supine SBP=157(16) mm Hg, DBP=100(5) mm Hg;
Perindopril 2‐8 mg twice daily: n=113(73 males,40 females); mean age=53(12) years; baseline upright SBP=150(15) mm Hg, DBP=101(6) mm Hg; baseline supine SBP=152(15) mm Hg, DBP=100(4) mm Hg;
Placebo: n=59(45 males,15 females); mean age=51(12) years; baseline upright SBP=161(14) mm Hg, DBP=103(8) mm Hg; baseline supine SBP=153(10) mm Hg, DBP=101(5) mm Hg

Interventions

Perindopril 4 mg once daily (wk 0‐4), perindopril 8 mg once daily (wk 4‐8), Perindopril 12 mg once daily (wk 8‐12), perindopril 16 mg once daily (wk 12‐16);
Perindopril 2 mg twice daily (wk 0‐4), perindopril 4 mg twice daily (wk 4‐8), perindopril 6 mg twice daily (wk 8‐12), perindopril 8 mg twice daily (wk 12‐16);
Placebo

Outcomes

Once daily dosing: upright and supine SBP/DBP 24 ± 2 h after last dose;
Twice daily dosing: upright and supine SBP/DBP 12 ± 2 h after last dose;
WDAE

Notes

Used week 4 supine data only; BP change reported, SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Figure 1, p. 481; BP measurement device not reported; Jadad score=3; funding source= RW Johnson Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Chrysant 1994

Methods

4‐week single‐blind placebo period; inclusion criteria= sitting DBP 100‐114 mm Hg after placebo period; 8‐week double‐blind treatment

Participants

Lisinopril 10 mg: n=85; mean age=54 years; baseline sitting SBP=154 mm Hg, DBP=104 mm Hg, HR=77 bpm; baseline upright SBP=154 mm Hg, DBP=103 mm Hg, HR=78 bpm;
Placebo: n=81; mean age=53 years; baseline sitting SBP=155 mm Hg, DBP=103 mm Hg, HR=77 bpm; baseline upright SBP=154 mm Hg, DBP=104 mm Hg, HR=79 bpm

Interventions

Lisinopril 10 mg once daily;
Placebo

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
Trough upright SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change not reported, endpoint BP reported and SEM reported; calculated endpoint SD from N and endpoint SEM; imputed endpoint SD for SD of change; BP data from Figure 1, p. 739; Jadad score=2; funding source= ICI Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Chrysant 1996

Methods

1‐week washout; 1‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg at 2 consecutive visits during run‐in, with a difference of 10 mm Hg or less between 2 visits; 6‐week double‐blind treatment

Participants

Benazepril 20 mg: n=42(28 males,14 females); mean age=53.7 years; baseline sitting SBP=153 mm Hg, DBP=104 mm Hg;
Placebo: n=40(22 males,18 females); mean age=53.5 years; baseline sitting SBP=153 mm Hg, DBP=103 mm Hg

Interventions

Benazepril 20 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in peak sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change reported and SE of change reported, endpoint BP reported; endpoint SD not reported, SD of change calculated from N and SE of change; BP data from Fagan abstract; SD of change data from Figure 1, p. 8; Jadad score=4; funding source= Ciba Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Cushman 1998

Methods

7‐day washout; 4‐week single‐blind placebo baseline; inclusion criteria= mean sitting DBP 95‐115 mm Hg of week 2 and week 4 baseline recordings with difference in these means </= 7 mm Hg, mean sitting SBP had to be < 210 mm Hg at each baseline visit; 12‐week double‐blind treatment

Participants

Enalapril 5 mg: n=144(94 males,50 females); mean age=56.1(10.0) years; baseline sitting SBP=155.2 mm Hg, DBP=101.6(5.5) mm Hg;
Placebo: n=150(104 males,46 females); mean age=55.8(11.4) years; baseline sitting SBP=155.4 mm Hg, DBP=101.6(5.6) mm Hg

Interventions

Enalapril 5 mg once daily;
Placebo;
administered between 6:30 AM and 10:00 AM

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported; endpoint BP reported; endpoint SD not reported; imputed overall trial mean SD of change for SBP and DBP; BP data from Table 2, p. 26; Jadad score=4; funding source= Merck

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
De Bruijn 1994

Methods

4‐week placebo run‐in; inclusion criteria= supine and standing DBP 95‐115 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

Trandolapril 0.5 mg: n=41(17 males,24 females); mean age=49(13) years; baseline SBP=163.8(12.8) mm Hg, DBP=99.5(5.8) mm Hg;
Trandolapril 1 mg: n=42(8 males,38 females); mean age=48(13) years; baseline SBP=159.9(14.3) mm Hg, DBP=99.9(5.2) mm Hg;
Trandolapril 2 mg: n=43(23 males,20 females); mean age=46(13) years; baseline SBP=161.1(13.1) mm Hg, DBP=99.8(5.9) mm Hg;
Placebo: n=44(18 males,26 females); mean age=50(7) years; baseline SBP=157.3(16.6) mm Hg, DBP=99.2(6.0) mm Hg

Interventions

Trandolapril 0.5 mg once daily;
Trandolapril 1 mg once daily;
Trandolapril 2 mg once daily;
Placebo;
administered in the morning

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change reported, endpoint BP and SD not reported; BP data from Figures 1 and 2, pp. S61‐S62; Jadad score=3; funding source= Roussel Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
DeQuattro 1997

Methods

4‐week placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg during final 2 wks of run‐in; 6‐week double‐blind treatment

Participants

Trandolapril 0.5 mg: n=41; baseline SBP=155.4(15.7) mm Hg, DBP=100.3(4.4) mm Hg;
Trandolapril 2 mg: n=67; baseline SBP=151.4(16.5) mm Hg, DBP=99.8(4.6) mm Hg;
Trandolapril 8 mg: n=43; baseline SBP=150.7(16.3) mm Hg, DBP=99.5(4.2) mm Hg;
Placebo: n=53; baseline SBP=154.8(15.1) mm Hg, DBP=100.3(4.6) mm Hg;
All patients (trandolapril monotherapy, verapamil monotherapy + verapamil/trandolapril combination treatment arms): n=726(456 males,270 females); mean age=54.7(10.9) years; baseline sitting SBP=151.8(16.2) mm Hg, DBP=100.4(6.1) mm Hg

Interventions

Trandolapril 0.5 mg once daily;
Trandolapril 2 mg once daily;
Trandolapril 8 mg once daily;
Placebo;
administered in the morning (8 AM ± 1 h)

Outcomes

Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Supine baseline BP reported in duplicate publication for each treatment arm; BP change reported, SD of change not reported, endpoint BP and SD not reported; imputed baseline SBP SD for SBP SD of change; imputed overall trial mean DBP SD of change; data from Table II, p. 367; duplicate publications=Levine 97, DeQuattro 97(NEJM); Jadad score=3; funding source= Knoll Pharma

Change in sitting SBP data is not the same as data reported in Levine 1997. Reviewers have decided to use data from DeQuattro 1997 (primary reference) because unadjusted endpoint data is provided. At this time, DBP data that is only available in Levine 1997 will not be used unless an explanation for the discrepancy in BP data is adequately explained by authors.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Drayer 1983

Methods

4‐ to 6‐week placebo run‐in; inclusion criteria= supine DBP 95‐115 mm Hg on 2 consecutive visits after beginning of placebo run‐in; 8‐week double‐blind treatment

Participants

Captopril 25 mg twice daily: n=77(60 males,17 females); mean age=52 years; baseline supine SBP=156 mm Hg, DBP=101 mm Hg;
Captopril 50 mg twice daily: n=71(50 males,21 females); mean age=52 years; baseline supine SBP=154 mm Hg, DBP=101 mm Hg;
Captopril 100 mg twice daily: n=69(44 males,25 females); mean age=55 years; baseline supine SBP=158 mm Hg, DBP=102 mm Hg;
Placebo: n=77(53 males,24 females); mean age=53 years; baseline supine SBP=157 mm Hg, DBP=102 mm Hg

Interventions

Captopril 25 mg twice daily;
Captopril 50 mg twice daily;
Captopril 100 mg twice daily;
Placebo

Outcomes

Percent change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change reported, SD of change not reported, endpoint BP and SD not reported; baseline SD not reported; imputed overall trial mean SD of change for SBP and DBP; percent change in SBP data from text, p. III‐110; percent change in DBP data from Figure 1, p. III‐110; percent change in BP has been converted to absolute BP change data; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Dupui 1993

Methods

Inclusion criteria= SBP 160‐210 mm Hg and DBP 95‐115 mm Hg based on 3 separate measurements over a period of several days; approximately 8‐week (60 days) double‐blind treatment

Participants

All patients: n=13(4 males,9 females);
Captopril 75 mg daily: n=8(3 males,5 females); mean age=63(9) years; baseline upright SBP=155.3(7.9) mm Hg, DBP=94.4(10.9) mm Hg; baseline lying SBP=164.3(10.4) mm Hg, DBP=96.5(10.7) mm Hg; baseline HR=64.5(10.7) bpm;
Placebo: n=5(1 male,4 females); mean age=63(4) years; baseline upright SBP=157.1(10.6) mm Hg, DBP=103.0(16.2) mm Hg; baseline lying SBP=168.1(7.0) mm Hg, DBP=100.4(11.1) mm Hg; baseline HR=66.2(4.9) bpm

Interventions

Captopril 75 mg daily (50 mg in the morning, 25 mg at bedtime);
Placebo

Outcomes

Upright SBP/DBP using Dynamap automated oscillometric device;
WDAE

Notes

BP change and SD of change not reported; endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Table III, p. 150; lying BP data also available; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Fairhurst 1994

Methods

3‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 100‐115 mm Hg, as determined by mean of 3 consecutive BP measurements using either mercury or random‐zero sphygmomanometer; 6‐week double‐blind treatment

Participants

All patients: n=283(157 males,126 females); mean age=55 years;
Spirapril 3 mg: n=55;
Spirapril 6 mg: n=61;
Spirapril 12 mg: n=58;
Spirapril 24 mg: n=49;
Placebo: n=60

Interventions

Spirapril 3 mg once daily;
Spirapril 6 mg once daily;
Spirapril 12 mg once daily;
Spirapril 24 mg once daily;
Placebo;
administered in the morning before breakfast

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change reported, SD of change not reported; endpoint BP and SD of change not reported; imputed overall trial mean SBP/DBP SD of change; BP data from Figure 1, p. 78; baseline BP for all patients is not reported; Jadad score=3; funding source= Sandoz Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Fernandez 1990

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 94‐114 mm Hg on 2 consecutive visits (one week apart) of run‐in; 4‐week double‐blind treatment

Participants

Cilazapril 1.25 mg: n=6(5 males,1 female); age=41(5) years; baseline sitting SBP=133(7) mm Hg, DBP=97(3) mm Hg, HR=77(5) bpm;
Cilazapril 2.5 mg: n=6(5 males,1 female); age=44(13) years; baseline sitting SBP=146(17) mm Hg, DBP=100(10) mm Hg, HR=77(13) bpm;
Cilazapril 5 mg: n=6(4 males,2 females); age=42(9) years; baseline sitting SBP=144(8) mm Hg, DBP=98(4) mm Hg, HR=72(8) bpm;
Placebo: n=6(3 males,3 females); age=48(8) years; baseline sitting SBP=150(10) mm Hg, DBP=101(3) mm Hg, HR=65(9) bpm

Interventions

Cilazapril 1.25 mg once daily;
Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo;
taken at 8 AM

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer;
Trough erect SBP/DBP using mercury sphygmomanometer;
Trough supine HR;
Trough erect HR;
WDAE

Notes

Only cilazapril 2.5 mg and placebo groups have BP >/= 140/90 mm Hg after placebo run‐in; used supine BP for cilazapril 2.5 mg and placebo groups only; BP change reported and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; data from Table 4, p. 55; Jadad score=3; funding source= Hoffman‐La Roche

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Fernandez 1994

Methods

4‐ to 5‐week single‐blind placebo run‐in; inclusion criteria= mean sitting DBP 95‐110 mm Hg at 2 consecutive visits 1 week apart; 8‐week double‐blind treatment

Participants

Fosinopril 20 mg: n=16(7 males,9 females); mean age=48.8(11.6) years; baseline sitting SBP=149.7(12.0) mm Hg, DBP=101.9(4.4) mm Hg, HR=72.9 bpm;
Placebo: n=17(2 males,15 females); mean age=53.2(7.0) years; baseline sitting SBP=146.6(9.9) mm Hg, DBP=100.3(3.7) mm Hg, HR=73.4 bpm

Interventions

Fosinopril 20 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change reported; endpoint BP and SD not reported; BP data from Table 2, p. I‐209; Jadad score=3; funding source= Bristol‐Myers Squibb

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Ford 1993

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= mean supine DBP 95‐115 mm Hg at 2 separate visits following discontinuation or tapering of antihypertensive medication (all patients had received antihypertensive therapy that was discontinued during the first 2 weeks of placebo run‐in); 4‐week double‐blind treatment; 1‐week single‐blind placebo washout period

Participants

Fosinopril 10 mg: n=17(4 males,13 females); mean age=49(9.1) years; baseline supine SBP=163.8 mm Hg, DBP=102.2 mm Hg; baseline HR=77.4 bpm;
Fosinopril 20 mg: n=15(6 males,9 females); mean age=55(8.1) years; baseline supine SBP=161.2 mm Hg, DBP=100.2 mm Hg; baseline HR=73.9 bpm;
Fosinopril 40 mg: n=16(9 males,7 females); mean age=51(9.6) years; baseline supine SBP=164.4 mm Hg, DBP=101.8 mm Hg; baseline HR=77.8 bpm;
Placebo: n=16(0 males,16 females); mean age=56(14) years; baseline supine SBP=154.7 mm Hg, DBP=99.8 mm Hg; baseline HR=74.2 bpm

Interventions

Fosinopril 10 mg once daily,
Fosinopril 20 mg once daily,
Fosinopril 40 mg once daily,
Placebo;
administered in morning

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer;
Trough HR;
WDAE

Notes

BP change and SD of change not reported, endpoint BP reported, endpoint SD not reported; imputed overall trial mean SBP and DBP SD of change; BP data from Table II, p. 327; trough and peak BP data also available in Figures 1 and 2, p.327; 2 sets of baseline BP are reported; Jadad score=3; funding source= Bristol‐Myers Squibb

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Gerritsen 1998

Methods

3‐week washout period; 4‐week placebo run‐in; inclusion criteria= sitting DBP 90‐115 mm Hg and SBP </= 200 mm Hg during run‐in; 8‐week double‐blind treatment, dosage of enalapril doubled after 4 weeks of treatment if DBP >/= 85 mm Hg

Participants

Enalapril 10 mg: n=40(28 males,12 females); mean age=58.8(9.5) years; baseline SBP=165(15) mm Hg, DBP=92(7.8) mm Hg, HR=81.2(13.3) bpm;
Placebo: n=41(26 males,15 females); mean age=61.9(7.8) years; baseline SBP=166(18) mm Hg, DBP=93(8.2) mm Hg, HR=81.2(14.3) bpm

Interventions

Enalapril 10 mg once daily;
Placebo;
administered in the morning

Outcomes

Trough sitting SBP/DBP using automated device (Dinamap);
WDAE

Notes

Used week 4 BP data only; BP change and SD of change not reported; endpoint BP and SD reported; imputed endpoint SD for SD of change; position of BP measurement not reported but likely sitting; BP data from Figure 1, p. 693; Jadad score=4; funding source= Bayer

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Gomez 1989

Methods

4‐week single‐blind placebo washout; inclusion criteria= supine DBP 95‐115 mm Hg after washout; 6‐week double‐blind treatment

Participants

Lisinopril 1.25 mg: n=41(38 males,3 females); mean age=58 years; baseline BP not reported for all randomized patients;
Lisinopril 5 mg: n=41(37 males,4 females); mean age=56 years; baseline BP not reported for all randomized patients;
Lisinopril 20 mg: n=44(42 males,2 females); mean age=54 years; baseline BP not reported for all randomized patients;
Lisinopril 80 mg: n=43(37 males,6 females); mean age=57 years; baseline BP not reported for all randomized patients;
Placebo: n=47(40 males,7 females); mean age=56 years; baseline BP not reported for all randomized patients

Interventions

Lisinopril 1.25 mg once daily;
Lisinopril 5 mg once daily;
Lisinopril 20 mg once daily
Lisinopril 80 mg once daily (patients received 40 mg once daily for the first 2 weeks and then 80 mg once daily for the last 4 weeks);
Placebo;
administered at 9 AM

Outcomes

Trough erect SBP/DBP using mercury sphygmomanometer;
Trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and 95% CI reported, endpoint BP reported, endpoint SD not reported; calculated SD of change from 95% CI; erect BP data from Table 3, p. 418; supine BP data from Table 2, p. 417; Jadad score=3; funding source= Merck Sharp & Dohme

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Gradman 1995

Methods

7‐day washout period; total 4‐week single‐blind placebo run‐in, patients' supine DBP >/= 95 mm Hg after initial 2‐week single‐blind placebo phase; additional 2‐week single‐blind placebo phase; inclusion criteria= mean supine DBP 100‐115 mm Hg, and two BP readings during weeks 2 and 4 of single‐blind placebo phase could not differ by > 7 mm Hg; 8‐week double‐blind treatment

Participants

Enalapril 20 mg: n=83(56 males,27 females); median age=53 years; baseline SBP=155.4 mm Hg, DBP=103.1 mm Hg;
Placebo: n=78(47 males,31 females); median age=53 years; baseline SBP=157.9 mm Hg, DBP=103.3 mm Hg

Interventions

Enalapril 20 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough supine SBP/DBP;
Mean change from baseline in peak supine SBP/DBP;
WDAE

Notes

BP change and SD of change reported, endpoint BP reported; endpoint SD not reported, BP data from Table 2, p. 1348; BP measurement device not reported; Jadad score=3; funding source= Merck

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Gradman 1997

Methods

4‐week single‐blind placebo baseline; inclusion criteria= sitting DBP 95‐115 mm Hg; 8‐week double‐blind treatment

Participants

All patients: n=707(457 males,250 females); mean age=53.5(10.5) years; baseline sitting SBP=155.5(17.7) mm Hg, DBP=101.9(5.7) mm Hg;
Enalapril 5 mg: n=85;
Enalapril 20 mg: n=48;
Placebo: n=79

Interventions

Enalapril 5 mg once daily;
Enalapril 20 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change reported; SD of change not reported; endpoint BP and SD not reported; baseline SBP SD for all groups reported; imputed baseline SBP SD for SD of change; imputed systematic review overall mean SD of change for DBP; DBP data from Figure 1, p. 432; SBP data from Figure 2, p. 433; Jadad score=3; funding source= Astra Merck, Inc.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Guitard 1994

Methods

3‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 100‐119 mm Hg; 6‐week double‐blind treatment

Participants

Spirapril 6 mg: n=66(32 males,34 females); mean age=58(11) years; baseline sitting SBP=171(12) mm Hg, DBP=106(4) mm Hg, HR=76(10) bpm;
Spirapril 12 mg: n=64(23 males,41 females); mean age=58(9) years; baseline sitting SBP=168(14) mm Hg, DBP=105(4) mm Hg, HR=73(9) bpm;
Spirapril 24 mg: n=66(35 males,31 females); mean age=58(11) years; baseline sitting SBP=170(12) mm Hg, DBP=106(4) mm Hg, HR=74(9) bpm;
Placebo: n=64(24 males, 40 females); mean age=57(11) years; baseline sitting SBP=167(11) mm Hg, DBP=105(3) mm Hg, HR=73(9) bpm

Interventions

Spirapril 6 mg once daily;
Spirapril 12 mg once daily;
Spirapril 24 mg once daily;
Placebo;
administered in the morning before breakfast

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change reported, SD of change reported but values are too low, endpoint SBP not reported, endpoint DBP reported, endpoint SD not reported; change in trough BP data from Table II, p. 83; SD of change data from Figure 2, p. 85; change in peak DBP data in subgroup of patients (from one study center) in Figure 3, p. 85; Table II provides data for both efficacy and intention‐to‐treat (ITT) analysis, ITT analysis BP data used instead of efficacy analysis BP data; imputed baseline SBP SD for SBP SD of change; imputed overall trial mean DBP SD of change; Jadad score=3; funding source= Sandoz Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Guitard 1997

Methods

4‐week placebo washout; inclusion criteria= mean DBP >/= 100 mm Hg at end of washout period and mean DBP 100‐115 mm Hg 24 hours after capsule intake during placebo phase; 8‐week double‐blind treatment, titrated to response at 4 weeks

Participants

Enalapril 5 mg: n=101(54 males,47 females); mean age=56.2(9.7) years; baseline SBP=163.2(16.4) mm Hg, DBP=99.5(6.1) mm Hg;
Spirapril 6 mg: n=101(50 males,50 females); mean age=58.0(7.9) years; baseline SBP=161.8(16.3) mm Hg, DBP=99.7(6.6) mm Hg;
Placebo: n=50(32 males,18 females); mean age=56.5(8.2) years; baseline SBP=161.3(18.2) mm Hg, DBP=98.2(6.9) mm Hg

Interventions

Enalapril 5 mg once daily;
Spirapril 6 mg once daily;
Placebo

Outcomes

Adjusted mean change from baseline in trough sitting DBP;
Adjusted mean change from baseline in peak sitting DBP

Notes

Used week 4 BP data only; BP change reported, SD of change not reported, endpoint BP reported, endpoint SD not reported; imputed overall trial mean DBP SD of change; DBP data from Table 5, p. 455; BP measurement device not reported; Jadad score=2; funding source= Novartis

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Guntzel 1991

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 100‐115 mm Hg at end of 3rd and 4th week of run‐in as well as during baseline BP profile (BP measured hourly during first 10 hours and last 4 hours after last placebo capsule); 8‐week double‐blind treatment

Participants

Cilazapril 2.5 mg: n=29(17 males,12 females); mean age=56(7) years; baseline DBP=103.5 mm Hg;
Cilazapril 5 mg: n=29(22 males,7 females); mean age=49(8) years; baseline DBP=103.1 mm Hg;
Placebo: n=27(17 males,10 females); mean age=52(9) years; baseline DBP=104.3 mm Hg

Interventions

Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo;
taken at 10 AM

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
Trough HR;
WDAE

Notes

Endpoint (week 8) BP change and DBP SE of change reported, endpoint BP and SD reported; BP also reported at weeks 4,6,8; calculated DBP SD of change from N and SE of change; imputed overall trial mean SBP SD of change; BP data from Figure 1, p. 10; Jadad score=3; funding source= Hoffman‐La Roche Ltd.

Duplication publication = Study 2 of Kobrin 1991.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Holwerda 1996

Methods

1‐week washout; 2‐week placebo run‐in; inclusion criteria= sitting DBP 95‐115 mm Hg after run‐in; 8‐week double‐blind treatment

Participants

Enalapril 20 mg: n=69(40 males,29 females); mean age=52.5(10.3) years; baseline sitting SBP=161.5(10.4) mm Hg, DBP=102.2(4.2) mm Hg;
Valsartan 80 mg: n=137(65 males,72 females); mean age=53.1(12.4) years; baseline sitting SBP=161.7(11.6) mm Hg, DBP=101.2(4.5) mm Hg;
Placebo: n=142(76 males,66 females); mean age=53.1(12.9) years; baseline sitting SBP=161.0(11.5) mm Hg, DBP=101.8(4.4) mm Hg

Interventions

Enalapril 20 mg once daily;
Valsartan 80 mg once daily;
Placebo;
taken in the morning

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Table 3, p. 1150; Jadad score=3; funding source= Ciba‐Geigy

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Homuth 1993

Methods

2‐week placebo run‐in; inclusion criteria= DBP 100‐115 mm Hg after run‐in; 6‐week double‐blind treatment

Participants

Ramipril 2.5 mg: n=40(26 males,14 females); mean age=47(10) years; baseline SBP=159(15) mm Hg, DBP=107(5) mm Hg;
Ramipril 5 mg: n=40(23 males,17 females); mean age=48(8) years; baseline SBP=159(13) mm Hg, DBP=107(6) mm Hg;
Ramipril 10 mg: n=40(24 males,16 females); mean age=47(9) years; baseline SBP=160(14) mm Hg, DBP=109(5) mm Hg;
Placebo: n=40(22 males,18 females); mean age=46(10) years; baseline SBP=161(17) mm Hg, DBP=109(5) mm Hg

Interventions

Ramipril 2.5 mg once daily;
Ramipril 5 mg once daily;
Ramipril 10 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change reported, SD of change not reported, endpoint BP and SD not reported; imputed baseline SBP SD for SBP SD of change; imputed overall trial mean DBP SD of change; BP data from Figures 1 and 2, p. 669; Jadad score=3; funding source= Cassella AG

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Kayanakis 1987

Methods

2‐week placebo run‐in; inclusion criteria= SBP 160‐200 mm Hg and DBP 95‐120 mm Hg at 2 consecutive measurements; 8‐week double‐blind treatment

Participants

Captopril 50 mg: n=42(23 males,19 females); mean age=52.8(10.6) years; baseline supine SBP=175.5(8.9) mm Hg, DBP=104.5(4.4) mm Hg;
Placebo: n=83(47 males,36 females); mean age=52.8(9.0) years; baseline supine SBP=172.0(7.7) mm Hg, DBP=102.5(3.8) mm Hg

Interventions

Captopril 50 mg once daily;
Placebo

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change for SBP and DBP; SBP data from Figure 1, p. 91S; DBP data from Figure 2, p. 91S; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Kobrin 1991

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 100‐115 mm Hg at last 2 visits of run‐in; 4‐week double‐blind treatment

Participants

Cilazapril 2.5 mg: n=29(18 males,11 females); mean age=50(9) years;
Cilazapril 5 mg: n=29(16 males,13 females); mean age=48(9) years;
Placebo: n=28(13 males,15 females); mean age=52(8) years

Interventions

Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough sitting DBP using mercury sphygmomanometer;
WDAE

Notes

SBP change not reported; DBP change and SE of change reported, endpoint BP and SD not reported; calculated DBP SD of change from N and SE of change; BP data from Table II, p. 34; Jadad score=3; funding source= Hoffman‐La Roche Ltd.

Kobrin 1991 reports results for 2 independent RCTs. Study 2 is same RCT as reported in Guntzel 1991. Data for Study 1 is entered as Kobrin 1991.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Koch 1999

Methods

1‐week washout; 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg at end of placebo run‐in; 12‐week double‐blind treatment

Participants

95 postmenopausal women taking HRT regimens that were held constant throughout experimental period;
Moexipril 15 mg: n=47; mean age=56.1(8.0) years; baseline sitting SBP=154.6(11.8) mm Hg, DBP=99.5(3.8) mm Hg, HR=72.7(7.7) bpm;
Placebo: n=48; mean age=57.0(6.8) years; baseline sitting SBP=158.5(13.6) mm Hg, DBP=100.0(3.7) mm Hg, HR=72.4(6.3) bpm

Interventions

Moexipril 15 mg once daily;
Placebo

Outcomes

Adjusted mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer

Notes

BP change reported, SD of change not reported, endpoint BP and SD not reported; baseline SD reported; imputed baseline SBP SD for SBP SD of change; imputed overall trial mean SD of change for DBP; change in BP data from text and Figure 1, p. 339; Jadad score=3; funding source= Schwarz Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Kohlmann Jr 1999

Methods

2‐week placebo run‐in; inclusion criteria= DBP 95‐115 mm Hg after run‐in; 8‐week double‐blind treatment

Participants

Trandolapril 2 mg: n=135(55 males,80 females); mean age=53.1(11.3) years; baseline SBP=157.3(15) mm Hg, DBP=101.0(6.3) mm Hg, HR=75.6(9.1) bpm;
Placebo: n=135(55 males,80 females); mean age=53.1(11.3) years; baseline SBP=156.1(18) mm Hg, DBP=100.3(6.6) mm Hg, HR=75.6(9.1) bpm

Interventions

Trandolapril 2 mg once daily;
Placebo

Outcomes

SBP/DBP

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; endpoint BP (week 8) data from text, p. 549; BP data for weeks 5 and 8 provided in Figures 1 and 2, p. 550; BP measurement device not reported; time of post‐dose BP measurement not reported; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Kostis 1991

Methods

2‐to 4‐week single‐blind placebo washout; inclusion criteria= supine DBP 95‐114 mm Hg after washout; 12‐week double‐blind treatment

Participants

Ramipril 1.25 mg: n=44(18 males,26 females); mean age=52.3 years; baseline SBP=159(15) mm Hg, DBP=99.9(3.7) mm Hg;
Ramipril 2.5 mg: n=43(27 males,16 females); mean age=49.4 years; baseline supine DBP=99.8(3.7) mm Hg;
Ramipril 5 mg: n=43(23 males,20 females); mean age=53.4 years; baseline supine DBP=100.7(5.1) mm Hg;
Ramipril 10 mg: 44(29 males,15 females); mean age=52.1 years; baseline supine DBP=101.2(4.4) mm Hg;
Placebo: n=42(22 males,20 females); mean age=51.3 years; baseline supine DBP=99.3(3.6) mm Hg

Interventions

Ramipril 1.25 mg once daily;
Ramipril 2.5 mg once daily;
Ramipril 5 mg once daily;
Ramipril 10 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough standing SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change reported, endpoint BP and SD not reported; BP data from Table 3, p. 13, SD data from Figures II and III, p. 12; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Krum 1992

Methods

3‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐115 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

All patients: n=22; mean age=59(11) years;
Cilazapril 2.5 mg: n=6; baseline sitting SBP=173(22) mm Hg, DBP=110(7.4) mm Hg;
Placebo: n=5; baseline sitting SBP=159(27) mm Hg, DBP=101(13.4) mm Hg

Interventions

Cilazapril 2.5 mg once daily;
Placebo;
taken at approximately 8 AM

Outcomes

Trough sitting SBP/DBP using oscillometric device (Dinamap);
Trough standing SBP/DBP using oscillometric device (Dinamap)

Notes

BP change and SD of change not reported, endpoint BP and SE reported; calculated endpoint SD from N and SE; endpoint SD values are too low; imputed SBP SD of change from baseline SBP SD of change, imputed overall trial mean DBP SD of change; BP data from Table 2, p. 455; Jadad score=2; funding source= Roche Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Krum 1998

Methods

4‐ to 6‐week placebo run‐in; inclusion criteria= mean sitting DBP 95‐115 mm Hg after run‐in, DBP could not differ by more than 7 mm Hg on 3 consecutive visits; 4‐week double‐blind treatment

Participants

Enalapril 20 mg: n=50(33 males,17 females); mean age=59(10) years; baseline SBP=161.9(14.3) mm Hg, DBP=102.2(5.0) mm Hg, HR=76.2(8.4) bpm;
Placebo: n=49(27 males,22 females); mean age=56(9) years; baseline SBP=158.3(14.1) mm Hg, DBP=101.7(4.5) mm Hg, HR=71.8(7.8) bpm

Interventions

Enalapril 20 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough sitting HR;
WDAE

Notes

BP change and SD of change reported; endpoint BP and SD not reported; SBP/DBP data from Table 2, p. 788; Jadad score=3; funding source= Hoffman‐La Roche

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Kuppers 1997

Methods

2‐week placebo run‐in; inclusion criteria= 1) sitting DBP=95‐114 mm Hg during last 2 weeks of run‐in, and also on day 0, the first day of active treatment, and 2) mean daytime (0600‐2159h) >/= 85mm Hg by ambulatory BP monitoring; consecutive measurements; 8‐week double‐blind treatment

Participants

Enalapril 10 mg once daily: n=77(32 males,45 females); mean age=55.8(8.7) years; baseline sitting SBP=166.8(14.8) mm Hg, DBP=106.7(4.6) mm Hg;
Placebo: n=77(33 males,44 females); mean age=57.2(9.5) years; baseline sitting SBP=166.4(14.1) mm Hg, DBP=106.9(4.7) mm Hg

Interventions

Enalapril 10 mg once daily,
Placebo;
administered at approximately 8AM

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Figure 1, p. 95; Jadad score=4; funding source= Solvay Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate
Kuschnir 1996

Methods

2‐to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 100‐120 mm Hg after run‐in; 8‐week double‐blind treatment

Participants

Benazepril 20 mg: n=77(32 males,45 females); mean age=55.8(8.7) years; baseline sitting SBP=166.8(14.8) mm Hg, DBP=106.7(4.6) mm Hg;
Placebo: n=77(33 males,44 females); mean age=57.2(9.5) years; baseline sitting SBP=166.4(14.1) mm Hg, DBP=106.9(4.7) mm Hg

Interventions

Benazepril 20 mg once daily;
Placebo;
administered at approximately 8 AM

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP reported, endpoint SD not reported, baseline SBP SD reported, imputed baseline SBP SD for SBP SD of change, imputed overall trial mean DBP SD of change; BP data from Table II, p. 1218; Jadad score=3; funding source= Ciba‐Geigy

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Lacourciere 1994

Methods

2‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐109 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

All patients: n=130; 102(79%) caucasian, 25(19%) black, 3(2%) oriental;
Cilazapril 2.5 mg: n=44(22 males,22 females); mean age=52.5(9.0) years; baseline sitting SBP=153.6(16.4) mm Hg, DBP=102.0(4.7) mm Hg;
Cilazapril 5 mg: n=42(31 males,11 females); mean age=50.4(9.1) years; baseline sitting SBP=154.8(15.1) mm Hg, DBP=101.0(4.3) mm Hg;
Placebo: n=44(29 males,15 females); mean age=53.6(8.5) years; baseline sitting SBP=157.5(15.8) mm Hg, DBP=101.1(3.8) mm Hg

Interventions

Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
Peak sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP reported, endpoint SD not reported; baseline SBP SD reported, imputed baseline SBP SD for SBP SD of change, imputed overall trial mean DBP SD of change; BP data from Table 3, p. 608; Jadad score=3; funding source= Hoffman‐La Roche Ltd.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Lerch 1999

Methods

4‐week placebo run‐in; inclusion criteria= supine DBP 90‐115 mm Hg after run‐in; 6‐week double‐blind treatment

Participants

Temocapril 20 mg: n=19(13 males,6 females); mean age=57.6(8.3) years; baseline SBP=162(22) mm Hg, DBP=98(9) mm Hg;
Placebo: n=11(8 males,3 females); mean age=56.1(5.6) years; baseline SBP=151(13) mm Hg, DBP=97(7) mm Hg

Interventions

Temocapril 20 mg once daily;
Placebo;
administered between 7 AM and 8 AM

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SE reported, calculated endpoint SD from N and endpoint SE, imputed endpoint SD for SD of change; BP data from Table 1, p. 529; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Levine 1995

Methods

2‐week placebo run‐in period; inclusion criteria= supine DBP >/= 95 mm Hg after run‐in; 12‐week double‐blind treatment, forced titration (dose doubled) every 4 weeks starting at 10 mg

Participants

Enalapril 10 mg: n=31(17 males,14 females); mean age=56 years; baseline SBP=152.5(13.4) mm Hg, DBP=102.5(5.0) mm Hg;
Placebo: n=29(17 males,12 females); mean age=53 years; baseline SBP=149.8(14.5) mm Hg, DBP=100.2(4.3) mm Hg

Interventions

Enalapril 10 mg once daily;
Placebo;
average dosing time 9 AM

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Used week 4 BP data only; BP change and SE of change reported, endpoint BP and endpoint SE reported, calculated SD of change from N and SE of change; SBP data from Table 2, p. 496; DBP data from Table 3, p. 497; Jadad score=3; funding source= Lederle Laboratories

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Luccioni 1988

Methods

2‐week placebo run‐in period; inclusion criteria= supine DBP >/= 95 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

All patients: n=40(31 males,9 females); mean age=56.6(9.5) years; baseline BP not reported for all patients

Interventions

Perindopril 2 mg once daily;
Perindopril 4 mg once daily;
Perindopril 8 mg once daily;
Placebo

Outcomes

Supine SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change not reported, endpoint BP and endpoint SE reported, calculated endpoint SD from N and endpoint SE, imputed endpoint SD for SD of change; BP data from Figure 2, p. 1133; time of BP measurement not reported (but most likely measured during the first 8 h post‐dose since ambulatory measurements were taken during that period); Jadad score=2; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
MacLean 1989

Methods

4‐week single‐blind placebo washout; inclusion criteria= sitting DBP >/= 95 mm Hg after washout; 12‐week double‐blind treatment, forced titration (dose doubled) every 4 weeks starting at 20 mg daily

Participants

Quinapril once daily: n=91(64 males,27 females); median age=49 years; baseline SBP=163 mm Hg, DBP=107 mm Hg;
Quinapril twice daily: n=90(61 males,29 females); median age=51 years; baseline SBP=164 mm Hg, DBP=106 mm Hg;
Placebo: n=89(56 males,33 females); median age=52 years; baseline SBP=162 mm Hg, DBP=105 mm Hg

Interventions

Quinapril 20, 40, 80 mg once daily (morning administration of active drug);
Quinapril 20, 40, 80 mg twice daily (2 capsules taken 12 h apart);
Placebo

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Used week 4 BP data only; BP change and SE of change reported, endpoint BP and SD not reported, calculated SD of change from N and change SE; BP data from Table III, p. 375; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Mancia 1992

Methods

4‐week placebo run‐in; inclusion criteria= supine and standing clinic DBP >/= 95 mm Hg after run‐in; 6‐week double‐blind treatment

Participants

Trandolapril 2 mg: n=42(31 males,11 females); mean age=51.4(9.7) years; baseline supine SBP=159.8(12.8) mm Hg, DBP=102.4(5.1) mm Hg, HR=72.1(8.3) bpm;
Placebo: n=20(15 males, 5 females); mean age=51.1(7.6) years; baseline supine SBP=158.0(13.5) mm Hg, DBP=102.3(4.8) mm Hg, HR=73.9(8.3) bpm

Interventions

Trandolapril 2 mg once daily;
Placebo;
administered at approximately 9 AM

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer;
Trough supine HR;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SE reported, calculated endpoint SD from N and SE; imputed endpoint SD for SD of change; BP data from Table II, p. 62D; duplicate publication=Ravogli 94; Jadad score=3; funding source= Roussel Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Mancia 1997

Methods

4‐week placebo run‐in; inclusion criteria= sitting DBP 100‐110 mm Hg at end of run‐in; 8‐week double‐blind treatment

Participants

Trandolapril 1 mg: n=50; mean age=51(10) years; baseline sitting SBP=159.3(12.4) mm Hg, DBP=103.6(3.1) mm Hg, HR=73.2(10.6) bpm;
Placebo: n=51; mean age=52(9) years; baseline sitting SBP=158.2(13.5) mm Hg, DBP=103.5(3.4) mm Hg, HR=75.4(8.2) bpm

Interventions

Trandolapril 1 mg once daily;
Placebo;
administered at approximately 9 AM after breakfast

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
Peak sitting SBP/DBP using mercury sphygmomanometer;
Trough sitting HR;
WDAE

Notes

BP change and SD of change not reported; endpoint BP and SD reported; imputed endpoint SD for SD of change; trough BP data from Table 1, p. 493; peak BP data (using 24h ambulatory BP monitoring) in Figure 3, p. 496; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
McCarron 1991

Methods

3‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= supine DBP 100‐114 mm Hg; 4‐week double‐blind treatment

Participants

Ramipril 10 mg: n=67(44 males,23 females); mean age=53.8(9.8) years; baseline supine SBP=152.7(11.4) mm Hg, DBP=102.9(3.0) mm Hg;
Placebo: n=33(23 males,10 females); mean age=52.3(11.7) years; baseline supine SBP=151.9(13.2) mm Hg, DBP=102.1(3.0) mm Hg

Interventions

Ramipril 10 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough standing SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SE of change reported, endpoint BP and SE reported, calculated SD of change from N and SE of change; BP data from Table III, p. 740; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
McFate‐Smith 1991

Methods

2‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐115 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

All patients: n=202; mean age=70 years; baseline sitting SBP=177 mm Hg, DBP=103 mm Hg;
Benazepril 2 mg BID: n=50;
Benazepril 10 mg BID: n=50;
Placebo: n=50

Interventions

Benazepril 2 mg twice daily;
Benazepril 10 mg twice daily;
Placebo

Outcomes

Mean change from baseline in sitting SBP/DBP;
BP measured 10‐14 h post‐dose

Notes

BP change reported; SD of change not reported, endpoint BP and SD not reported; imputed overall trial mean SD of change; BP data from Table 1, p. IV‐81; BP measurement device not reported; Jadad score=3; funding source= Ciba‐Geigy Inc.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Messerli 1998

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg after run‐in; 6‐week double‐blind treatment

Participants

Trandolapril 4 mg: n=159(106 males,53 females); mean age=54.3 years; baseline SBP=151.8(14.8) mm Hg, DBP=101.3(5.0) mm Hg;
Placebo: n=152(103 males,49 females); mean age=53.8 years; baseline SBP=153.6(13.4) mm Hg, DBP=100.5(4.5) mm Hg

Interventions

Trandolapril 4 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change reported, endpoint BP and SD not reported; SD of change values reported are low; imputed baseline SBP SD for SBP SD of change, imputed overall trial mean DBP SD of change; BP data from Table 2, p. 325; Jadad score=3; funding source= Knoll Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Moser 1991

Methods

2‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg on 2 consecutive visits (weeks 2 and 4 of run‐in) with </= 10 mm Hg difference between 2 visits; 4‐week double‐blind treatment

Participants

Benazepril 2 mg once daily: n=34(24 males,10 females); mean age=50.4 years; baseline sitting SBP=151.6(15.9) mm Hg, DBP=102.1(5.6) mm Hg;
Benazepril 5 mg once daily: n=38(23 males,15 females); mean age=51.1 years; baseline sitting SBP=152.7(15.2) mm Hg, DBP=101.2(5.3) mm Hg;
Benazepril 10 mg once daily: n=34(23 males,11 females); mean age=51.9 years; baseline sitting SBP=153.1(13.7) mm Hg, DBP=101.8(5.7) mm Hg;
Benazepril 20 mg once daily: n=36(23 males,13 females); mean age=50.4 years; baseline sitting SBP=151.9(15.7) mm Hg, DBP=101.7(4.7) mm Hg;
Placebo: n=31(21 males,10 females); mean age=48.2 years; baseline sitting SBP=150.7(14.3) mm Hg, DBP=101.7(4.9) mm Hg

Interventions

Benazepril 2 mg once daily;
Benazepril 5 mg once daily;
Benazepril 10 mg once daily;
Benazepril 20 mg once daily;
Placebo

Outcomes

Trough sitting DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SE reported, calculated endpoint SD from N and endpoint SE, imputed endpoint SD for SD of change; DBP data from Table III, p. 325; Jadad score=3; funding source= Ciba‐Geigy

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Mroczek 1991

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg at each of last 2 visits during run‐in; 4‐week double‐blind treatment

Participants

Cilazapril 2.5 mg: n=59(45 males,14 females); mean age=52.4 years; baseline sitting SBP=146.3 mm Hg, DBP=101.1 mm Hg, HR=75.5 bpm;
Cilazapril 5 mg: n=59(41 males,18 females); mean age=52.9 years; baseline sitting SBP=148.4 mm Hg, DBP=101.3 mm Hg, HR=76.2 bpm;
Cilazapril 10 mg: n=58(34 males,24 females); mean age=50.3 years; baseline sitting SBP=144.3 mm Hg, DBP=100.8 mm Hg, HR=75.1 bpm;
Placebo: n=59(36 males,23 females); mean age=54.0 years; baseline sitting SBP=149.8 mm Hg, DBP=100.7 mm Hg, HR=77.3 bpm

Interventions

Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Cilazapril 10 mg once daily;
Placebo;
taken in the morning after light breakfast

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough sitting HR;
WDAE

Notes

BP change and SE of change reported, endpoint BP and SE reported; calculated SD of change from N and SE of change; BP data from text and Table 2, p. 1424; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Mroczek 1996

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg at last 2 consecutive visits of placebo run‐in, with difference between visits of 10 mm Hg or less; 12‐week double‐blind treatment

Participants

Moexipril 7.5 mg: n=51(31 males,20 females); mean age=54.9 years; baseline sitting SBP=152.2 mm Hg, DBP=101.8 mm Hg, HR=75.8 bpm; baseline standing SBP=148.4 mm Hg, DBP=100.9 mm Hg;
Moexipril 15 mg: n=47(30 males,17 females); mean age=56.0 years; baseline sitting SBP=154.0 mm Hg, DBP=100.9 mm Hg, HR=73.6 bpm; baseline standing SBP=150.4 mm Hg, DBP=100.2 mm Hg;
Placebo: n=51(37 males,14 females); mean age=55.3 years; baseline sitting SBP=154.2 mm Hg, DBP=101.2 mm Hg, HR=74.7 bpm; baseline standing SBP=150.9 mm Hg, DBP=101.1 mm Hg

Interventions

Moexipril 7.5 mg once daily;
Moexipril 15 mg once daily;
Placebo

Outcomes

Adjusted mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Trough sitting DBP using mercury sphygmomanometer;
Trough standing SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change reported; endpoint SBP not reported, endpoint DBP reported, endpoint SD not reported; change in SBP data from Table 3, p. 85; change in DBP data from Table 2, p. 83; Jadad score=3; funding source= Schwarz Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Muiesan 1987

Methods

3‐week placebo run‐in; inclusion criteria= supine DBP 100‐110 mm Hg during run‐in; 4‐week double‐blind treatment

Participants

All patients: n=152(77 males,75 females); mean age=69(4) years;
Captopril 25 mg: n=52; baseline standing SBP=173(13) mm Hg, DBP=106(5) mm Hg; baseline supine SBP=176(14) mm Hg, DBP=105(5) mm Hg;
Placebo: n=50; baseline standing SBP=172(14) mm Hg, DBP=106(5) mm Hg; baseline supine SBP=176(14) mm Hg, DBP=104(5) mm Hg;

Interventions

Captopril 25 mg twice daily;
Placebo

Outcomes

Standing SBP/DBP using mercury sphygmomanometer;
Supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change in captopril group; imputed baseline SBP SD for SBP SD of change in placebo group; in placebo group, imputed systematic review overall mean SD of change for DBP; BP data from text and Figure 1, p. S600; baseline supine SBP/DBP and SD for placebo group from Table 1, p. S601; supine BP data also available; Jadad score=3; funding source= Squibb Italia SpA

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Myers 1996

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= supine DBP 95‐114 mm Hg after run‐in; 12‐week double‐blind treatment; 293 patients included in safety analysis; 260 patients included in efficacy analyses

Participants

Perindopril 2 mg: n=62(39 males,23 females); mean age=51(16) years; baseline SBP/DBP not reported for all 62 patients;
Perindopril 4 mg: n=57(32 males,25 females); mean age=51(15) years; baseline SBP/DBP not reported for all 57 patients;
Perindopril 8 mg: n=59(32 males,27 females); mean age=51(15) years; baseline SBP/DBP not reported for all 59 patients;
Perindopril 16 mg: n=57(35 males,22 females); mean age=51(15) years; baseline SBP/DBP not reported for all 57 patients;
Placebo: n=58(30 males,28 females); mean age=53(15) years; baseline SBP/DBP not reported for all 58 patients

Interventions

Perindopril 2 mg once daily;
Perindopril 4 mg once daily;
Perindopril 8 mg once daily;
Perindopril 16 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in peak supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change reported, SD of change not reported, endpoint BP and SD not reported, baseline SEM reported, calculated baseline SD from N and baseline SEM, imputed baseline SBP SD for SBP SD of change; imputed overall trial mean DBP SD of change; BP data from Table 2, p. 1193; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
New 2000

Methods

No placebo run‐in; inclusion criteria= patients with established Type 2 DM and BP > 75th centile for age and sex, taking no anti‐hypertensive medication; 3‐week double‐blind treatment

Participants

Trandolapril 4 mg: n=12(10 males,2 females); mean age=58(11) years; baseline SBP=168(13) mm Hg, DBP=98(10) mm Hg;
Placebo: n=12(9 males,3 females); mean age=60(12) years; baseline SBP=165(14) mm Hg, DBP=93(6) mm Hg

Interventions

Trandolapril 4 mg once daily;
Placebo;
administered at 8 AM

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change not reported; endpoint BP and SD reported; imputed endpoint SD for SD of change; SBP/DBP data from Figure 1, p. 137; Jadad score=2; funding source= Hoechst Marion Rousell

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Oparil 1999

Methods

4‐ to 5‐week single‐blind placebo run‐in during which previous antihypertensive medication withdrawn; patients qualified for 3‐ to 4‐week enalapril challenge period if sitting DBP 95‐114 mm Hg and difference between their average sitting DBP values for last 2 visits of placebo run‐in period did not exceed 12 mm Hg; during enalapril challenge patients received enalapril 20 mg daily (10 mg for first 3 days); patients who developed persistent, nonproductive cough while receiving enalapril were then given placebo for 2‐4 weeks to allow cough to clear; eligible patients (those meeting inclusion criteria for enalapril challenge and whose cough subsequently cleared during placebo washout period) then entered 6‐week double‐blind treatment

Participants

Enalapril 20 mg: n=45(23 males,22 females); baseline sitting SBP=154.6(14.1) mm Hg, DBP=100.9(4.7) mm Hg, HR=74.8(9.4) bpm;
Placebo:n=45(21 males,24 females); baseline sitting SBP=154.1(14.1) mm Hg, DBP=99.8(4.0) mm Hg, HR=74.4(8.1) bpm

Interventions

Enalapril 20 mg once daily (10 mg for first 3 days);
Placebo

Outcomes

Mean change from baseline in sitting DBP;
WDAE

Notes

DBP change and SD of change reported, endpoint BP and SD not reported, DBP data from text (p. 8) and Figure 3, p. 10; BP measurement device not reported; time of BP measurement not reported; Jadad score=4; funding source= SmithKline Beecham Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Overlack 1994

Methods

3‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐104 mm Hg after run‐in; 6‐week double‐blind treatment

Participants

Perindopril 4 mg: n=253(130 males,123 females); mean age=59.3(11.1) years; baseline SBP=161.7(17.5) mm Hg, DBP=99.4(4.8) mm Hg, HR=78.5(14.3) bpm;
Placebo: n=237(133 males,104 females); mean age=59.1(10.8) years; baseline SBP=160.3(16.9) mm Hg, DBP=99.5(4.6) mm Hg, HR=79.3(13.9) bpm

Interventions

Perindopril 4 mg once daily;
Placebo;
administered in the morning

Outcomes

Trough sitting SBP/DBP using automatic device;
HR

Notes

BP change and SD of change not reported, endpoint BP and SEM reported, calculated endpoint SD from N and endpoint SEM, imputed endpoint SD for SD of change; BP data from Table III, p. 129; Jadad score=3; funding source= Servier

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Persson 1996

Methods

Washout phase; 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg, with a difference of 10 mm Hg or less at last 2 consecutive visits of run‐in; subjects with DBP =/> 110 mm Hg could be included directly following minimum of 7 days single‐blind placebo; 8‐week double‐blind treatment

Participants

Moexipril 7.5 mg: n=50(21 males,29 females); mean age=70.4 years; baseline sitting SBP=173 mm Hg, DBP=102 mm Hg, HR=76.7 bpm;
Moexipril 15 mg: n=53(31 males,22 females); mean age=69.2 years; baseline sitting SBP=169 mm Hg, DBP=102 mm Hg, HR=73.9 bpm;
Placebo: n=48(33 males,15 females); mean age=70.7 years; baseline sitting SBP=172 mm Hg, DBP=103 mm Hg, HR=72.7 bpm

Interventions

Moexipril 7.5 mg once daily;
Moexipril 15 mg once daily;
Placebo

Outcomes

Adjusted mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Placebo‐corrected adjusted change from baseline in peak sitting DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change reported, endpoint SBP not reported, endpoint DBP reported, endpoint SD not reported; change in trough BP data from Table 2, p. 261; placebo‐corrected change in peak DBP data from Table 4, p. 262; endpoint BP data used instead of weighted mean of BP change for 3 measurements (at weeks 4,6,8) because N values not reported for weeks 4 and 6; Jadad score=3; funding source= Schwarz Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Pittrow 1997

Methods

2‐week washout; 2‐week single‐blind placebo run‐in; inclusion criteria= mean sitting DBP 100‐114 mm Hg; 6‐week double‐blind treatment phase at fixed dose, patients with inadequate BP response had their doses doubled and were treated for another 6 weeks

Participants

Spirapril 3 mg: n= 52(32 males,20 females); mean age=55.8 years; baseline sitting SBP=159.0 mm Hg, DBP=104.6 mm Hg (trough data); baseline sitting SBP=156.7 mm Hg, DBP=103.4 mm Hg (peak data);
Spirapril 6 mg: n= 52(28 males,24 females); mean age=53.6 years; baseline sitting SBP=159.0 mm Hg, DBP=104.8 mm Hg (trough data); baseline sitting SBP=157.6 mm Hg, DBP=102.9 mm Hg (peak data);
Placebo: n= 26(18 males,8 females); mean age=54.2 years; baseline sitting SBP=154.2 mm Hg, DBP=104.1 mm Hg (trough data); baseline sitting SBP=151.6 mm Hg, DBP=102.8 mm Hg (peak data)

Interventions

Spirapril 3 mg once daily;
Spirapril 6 mg once daily;
Placebo;
taken in the morning before breakfast

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in peak sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Used week 6 BP data only; BP change and SD of change reported, endpoint BP reported, endpoint SD not reported; change in trough and peak BP data from Table 2A, p. 624; Jadad score=3; funding source= Novartis Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Pizarro 1996

Methods

2‐week placebo run‐in; inclusion criteria= mean sitting DBP 95‐110 mm Hg; 6‐week double‐blind treatment

Participants

Fosinopril 20 mg: n=16(4 males,12 females); mean age=56.4(8.1) years; baseline sitting SBP=151.8(14.0) mm Hg, DBP=100.8(4.8) mm Hg, HR=75.9(11.9) bpm;
Placebo: n=18(2 males,15 females); mean age=53.2(7.0) years; baseline sitting SBP=160.1(22.1) mm Hg, DBP=100.1(2.4) mm Hg, HR=72.3(6.1) bpm

Interventions

Fosinopril 20 mg once daily;
Placebo

Outcomes

Trough sitting SBP/DBP;
Trough HR;
WDAE

Notes

SBP change not reported, DBP change reported; SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from text, p. 496 and p. 460; BP measurement device not reported; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Poirier 1991

Methods

2‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐109 mm Hg, within 10 mm Hg on 2 consecutive weekly visits during run‐in; 4‐week double‐blind treatment

Participants

All patients: n=42(27 males,15 females); all white;
Cilazapril 2.5 mg: n=14; mean age=53.6(8.0) years; baseline sitting SBP=153.6(16.4) mm Hg, DBP=102.0(4.7) mm Hg;
Cilazapril 5 mg: n=14; mean age=53.1(8.2) years; baseline sitting SBP=154.8(15.1) mm Hg, DBP=101.0(4.3) mm Hg;
Placebo: n=14; mean age=55.1(7.7) years; baseline sitting SBP=157.5(15.8) mm Hg, DBP=101.1(3.8) mm Hg

Interventions

Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo;
taken in the morning

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change not reported, endpoint BP reported, endpoint SD not reported; baseline SBP SD reported, imputed baseline SBP SD for SBP SD of change, imputed overall trial mean DBP SD of change; BP data from Table 1, p. 914; Jadad score=3; funding source= Hoffman‐La Roche Ltd.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Pool 1990

Methods

4‐ to 6‐week placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg on 2 consecutive visits after beginning of placebo run‐in; 4‐week double‐bind treatment at fixed dose; after 4 weeks, patients with inadequate BP response had their doses doubled during the second 4 weeks; hydrochlorothiazide 25 mg was added during final 4 weeks

Participants

All patients: n=418 patients randomized to double‐blind treatment; n=380 who completed 4 weeks of double‐blind treatment included in efficacy analysis;
Fosinopril 5 mg: n=83 randomized; for efficacy analysis n=74(53 males,21 females); mean age=53.2 years; baseline sitting SBP=151.7 mm Hg, DBP=101.4 mm Hg;
Fosinopril 10 mg: n=84 randomized; for efficacy analysis n=71(55 males,16 females); mean age=53.5 years; baseline sitting SBP=148.6 mm Hg, DBP=100.9 mm Hg;
Fosinopril 20 mg: n=84 randomized; for efficacy analysis n=79(51 males,28 females); mean age=54.2 years; baseline sitting SBP=153.2 mm Hg, DBP=102.4 mm Hg;
Fosinopril 40 mg: n=85 randomized; for efficacy analysis n=79(52 males, 27 females); mean age=50.9 years; baseline sitting SBP=153.0 mm Hg, DBP=102.2 mm Hg;
Placebo: n=82 randomized; for efficacy analysis n=77(52 males,25 females); mean age=53.2 years; baseline sitting SBP=151.7 mm Hg, DBP=101.4 mm Hg

Interventions

Fosinopril 5 mg once daily;
Fosinopril 10 mg once daily;
Fosinopril 20 mg once daily;
Fosinopril 40 mg once daily;
Placebo

Outcomes

Mean change in trough sitting SBP/DBP using mercury sphygmomanometer;
Mean change in trough standing SBP/DBP using mercury sphygmomanometer

Notes

BP change reported, SD of change not reported, endpoint BP and SD not reported; baseline SD not reported; imputed overall trial mean SD of change for SBP and DBP; change in SBP data from Figure 2, p. 524; change in DBP data from Table II, p. 526; Jadad score=3; funding source= Bristol‐Myers Squibb

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Pool 1997

Methods

4‐ to 5‐week single‐blind placebo run‐in; inclusion criteria= mean sitting DBP 95‐110 mm Hg at consecutive visits (third and fourth weeks, or fourth and fifth weeks) during run‐in; 8‐week double‐blind treatment

Participants

All patients: n=548(335 males,213 females); mean age=51.5(11.0) years; baseline sitting SBP=149.5(15.7) mm Hg, DBP=100.1(4.0) mm Hg;
Fosinopril 2.5 mg: n=33 randomized; BP data reported for n=29; baseline sitting SBP=153.0 mm Hg, DBP=100.4 mm Hg;
Fosinopril 10 mg: n=30 randomized; BP data reported for n=29; baseline sitting SBP=147.4 mm Hg, DBP=99.6 mm Hg;
Fosinopril 40 mg: n=32 randomized; BP data reported for n=28; baseline sitting SBP=147.2 mm Hg, DBP=98.6 mm Hg;
Placebo: n=32 randomized; BP data reported for n=29; baseline sitting SBP=150.4 mm Hg, DBP=99.8 mm Hg

Interventions

Fosinopril 2.5 mg once daily;
Fosinopril 10 mg once daily;
Fosinopril 40 mg once daily;
Placebo

Outcomes

Adjusted mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Adjusted BP change reported, SD of change not reported, endpoint BP reported; endpoint SD not reported; baseline SD not reported; imputed overall trial mean SD of change for SBP and DBP; used endpoint BP data to calculated change in BP instead of entering adjusted BP change data; BP data from Tables 3 and 4, p. 120; Jadad score=3; funding source= Bristol‐Myers Squibb

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Pool 2001

Methods

2‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 100‐115 mm Hg after run‐in; 8‐week double‐blind treatment

Participants

All patients: n=454(286 males,168 females); mean age=53.8 years;
Benazepril 10 mg: n=116; baseline SBP=155.3 mm Hg, DBP=104.2 mm Hg, HR=74.2 bpm;
Placebo: n=115; baseline SBP=156.1 mm Hg, DBP=105.1 mm Hg, HR=74.4 bpm

Interventions

Benazepril 10 mg once daily;
Placebo;
administered at approximately 8 AM

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough sitting HR;
WDAE

Notes

BP change reported, SD of change not reported; endpoint BP and SD not reported, baseline SD not reported, imputed overall trial mean SBP and DBP SD of change; BP and HR data from Table 1, p. 497; Jadad score=5; funding source= Novartis Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate
Pordy 1994

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐115 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

Cilazapril 0.5‐10 mg: n=288(166 males,122 females); mean age=53.9(12.1) years; baseline sitting DBP=100.4 mm Hg;
Placebo: n=97(57 males,40 females); mean age=53.0(11.9) years; baseline sitting DBP=100.3 mm Hg

Interventions

Cilazapril 0.5 mg once daily;
Cilazapril 5 mg once daily;
Cilazapril 10 mg once daily;
Placebo;
taken between 8 AM and 10 AM

Outcomes

Mean change from baseline in trough sitting DBP using mercury sphygmomanometer;
WDAE

Notes

SBP not reported; DBP change and SD of change reported, endpoint BP and SD not reported; BP data from Table 3, p. 315; Jadad score=3; funding source= Hoffmann‐La Roche Ltd.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Prager 1994

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= DBP 95‐115 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

Cilazapril 2.5 mg: n=54(36 males,18 females); mean age=55.6(10.1) years; baseline sitting SBP=162.5(15.1) mm Hg, DBP=102.4(5.4) mm Hg;
Cilazapril 5 mg: n=55(32 males,23 females); mean age=55.6(10.8) years; baseline sitting SBP=158.8(16.5) mm Hg, DBP=100.8(4.3) mm Hg;
Placebo: n=53(29 males,24 females); mean age=58.1(9.5) years; baseline sitting SBP=161.4(16.5) mm Hg, DBP=102.1(5.7) mm Hg

Interventions

Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo;
taken in the morning

Outcomes

Trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Table 2, p. S95; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Prichard 2002

Methods

4‐week placebo run‐in; inclusion criteria= 1) sitting DBP=95‐114 mm Hg and sitting SBP</=200mm Hg during 2 weeks immediately prior to randomization, and on day 0, the first day of active treatment, with variation in DBP of not more than 10 mm Hg between the last week of run‐in phase and day 0, and 2) mean daytime (0600‐2159h) DBP>/=85 mm Hg by ambulatory BP monitoring on day immediately preceding randomization; 8‐week double‐blind treatment

Participants

Enalapril 20 mg once daily: n=53(35 males,18 females); mean age=52.2(10.3) years; baseline sitting SBP=165.2(14.5) mm Hg, DBP=101.1(4.4) mm Hg; baseline HR=78.0(7.3) bpm;
Placebo: n=50(29 males,21 females); mean age=53.7(8.7) years; baseline sitting SBP=162.8(14.5) mm Hg, DBP=99.9(3.9) mm Hg; baseline HR=76.6(8.8) bpm

Interventions

Enalapril 20 mg once daily,
Placebo;
administered in morning (8.00+/‐2 h)

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change reported, endpoint BP and SD reported, BP data from Table II, p. 169; Jadad score=4; funding source= Solvay Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate
Reimann 1995

Methods

3‐week placebo run‐in; inclusion criteria= DBP 95‐104 mm Hg; 6‐week double‐blind treatment

Participants

Perindopril 4 mg: n=27(20 males,7 females); mean age=54(9.8) years; baseline sitting SBP=161.3(12.5) mm Hg, DBP=100.4(3.8) mm Hg;
Placebo: n=26(14 males,12 females); mean age=55(8.5) years; baseline sitting SBP=159.6(17.3) mm Hg, DBP=100.7(3.2) mm Hg

Interventions

Perindopril 4 mg once daily;
Placebo

Outcomes

SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Table 3, p. 190; time and position of BP measurement not reported; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Roca‐Cusachs 2001

Methods

1‐week washout (only for patients previously treated with anti‐hypertensive therapy); 2‐week single‐blind placebo run‐in; inclusion criteria= DBP 90‐109 mm Hg (which differed < 10mm Hg from that observed in previous visit) after run‐in; 6‐week double‐blind treatment

Participants

All patients (per protocol population): n=342(137 males,205 females); mean age=55.6(9.9) years; baseline sitting SBP=158.3(10.6) mm Hg, DBP=98.6(5.3) mm Hg

Interventions

Enalapril 5 mg once daily;
Enalapril 10 mg once daily;
Enalapril 20 mg once daily;
Placebo;
taken in the morning;
patients assigned to receive either 10 or 20 mg received 5 mg for the first week of treatment before titration to dose assigned

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change not reported, endpoint BP reported; endpoint SD not reported; baseline SD reported; imputed baseline SBP SD for SD of change; imputed overall trial mean DBP SD of change; BP data from Figure 1, p. 844; Jadad score=2; funding source= VITA INVEST

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Sassano 1984

Methods

15‐day washout; 15‐day placebo run‐in; inclusion criteria= DBP 95‐120 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

Enalapril 20 mg: n=53(40 males,13 females); mean age=47.4 years; baseline supine SBP=161.4(13.0) mm Hg, DBP=103.3(6.3) mm Hg;
Placebo: n=47(31 males,16 females); mean age=46.8 years; baseline supine SBP=163.5(13.8) mm Hg, DBP=104.6(7.0) mm Hg

Interventions

Enalapril 20 mg once daily;
Placebo

Outcomes

Peak supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Table I, p. 19; Jadad score=3; funding source= Merck Sharpe and Dohme

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Saynavalammi 1988

Methods

4‐week single‐blind placebo phase; inclusion criteria= DBP 100‐115 mm Hg after placebo phase; 12‐week double‐blind treatment, dosage doubled every 4 weeks (10‐40 mg twice daily)

Participants

Quinapril: n=7(2 males,5 females); mean age=48(11) years; baseline SBP=159(8) mm Hg, DBP=105(3) mm Hg;
Placebo: n=7(3 males,4 females); mean age=47(13) years; baseline SBP=162(21) mm Hg, DBP=105(5) mm Hg

Interventions

Quinapril 10 mg twice daily;
Placebo

Outcomes

Trough (12h after previous dose) sitting SBP/DBP using mercury sphygmomanometer

Notes

Used week 4 BP data only; BP change and SD of change not reported, endpoint BP and SEM reported, calculated endpoint SD from N and endpoint SEM, imputed endpoint SD for SD of change; BP data from Figure 2, p. 90; Jadad score=2; funding source= Warner‐Lambert/Parke‐Davis Co.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Schoenberger 1986

Methods

4‐ to 6‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 92‐109 mm Hg on last 2 visits of run‐in; 4‐week double‐blind treatment at fixed dose, after 4‐weeks captopril dosage doubled in all randomized patients for additional 4 weeks

Participants

Captopril 50 mg once daily: n=88(58 males,30 females); mean age=52 years; baseline sitting SBP=149.3 mm Hg, DBP=98.2 mm Hg;
Captopril 50 mg twice daily: n=91(60 males,31 females); mean age=52 years; baseline sitting SBP=151.2 mm Hg, DBP=100.1 mm Hg;
Placebo: n=90(58 males,32 females); mean age=51 years; baseline sitting SBP=148.7 mm Hg, DBP=98.5 mm Hg

Interventions

Captopril 50 mg once daily;
Captopril 50 mg twice daily;
Placebo;
patients in daily schedule groups received their active medication in the morning and placebo in the evening

Outcomes

Sitting DBP

Notes

Used week 4 BP data only; BP change not reported, SD of change not reported, endpoint SBP not reported; endpoint DBP reported; endpoint SD not reported; baseline SD not reported; imputed overall trial mean SD of change for DBP; DBP data from Table 3, p. 382; BP measurement device not reported; Jadad score=2; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Scholze 1998

Methods

1‐week washout period (for patients previously treated with antihypertensive therapy); 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 100‐115 mm Hg (which differed by less than 10 mm Hg from that observed on the previous visit) after run‐in; 6‐week double‐blind treatment

Participants

Trandolapril 0.5‐2 mg: n=85; baseline SBP/DBP not reported;
Placebo: n=30; baseline SBP/DBP not reported

Interventions

Trandolapril 0.5 mg once daily;
Trandolapril 1 mg once daily;
Trandolapril 2 mg once daily;
Placebo;
administered with or immediately after breakfast

Outcomes

Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Adjusted and non‐adjusted BP data reported; non‐adjusted BP entered in Revman; BP change reported, SD of change not reported; 95% confidence interval of change reported; endpoint BP and SD not reported; calculated SD of change from 95% CI of change; BP data from Table 1, p. 493; Jadad score=3; funding source= Knoll AG

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Scholze 1999

Methods

2‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= supine DBP 100‐115 mm Hg after run‐in; 6‐week double‐blind treatment

Participants

All patients: n=507(327 males,180 females); mean age=50.2 years; baseline SBP/DBP not reported

Interventions

Ramipril 2.5 mg once daily;
Ramipril 5 mg once daily;
Ramipril 10 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer

Notes

BP change and SEM of change reported, endpoint BP and SD not reported; calculated SD of change from N and change SE; BP data from Table 1, p. 1453; Jadad score=3; funding source= Hoechst AG

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Simon 1983

Methods

4‐week placebo run‐in; inclusion criteria= not reported but baseline DBP for all groups is at least 90 mm Hg; 12‐week total double‐blind treatment; increasing doses of enalapril 10, 20, and 40 mg daily every 4 weeks

Participants

All patients: n= 34(33 male,1 female) white patients;
Enalapril once and twice daily: n=21; mean age=52(11) years; baseline SBP=143(15) mm Hg, DBP=93(5) mm Hg;
Placebo: n=12; mean age=50(17) years; baseline SBP=150(14) mm Hg, DBP=92(7) mm Hg

Interventions

Enalapril 10 mg once daily;
Enalapril 10 mg twice daily;
Placebo;
first dose taken in the morning

Outcomes

Trough sitting SBP/DBP

Notes

Used week 4 DBP only since patients treated with enalapril 10 mg once daily did not have SBP >/= 140mm Hg at baseline; BP change and SD of change not reported; endpoint BP reported; endpoint SD not reported; imputed overall trial mean SD of change; BP data from Figure 1, p. 461; BP measurement device not reported; Jadad score=2; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Smith 1998

Methods

2‐ to 3‐week screening/washout period; 4‐week single‐blind placebo run‐in; inclusion criteria= supine DBP 95‐114 mm Hg; 12‐week double‐blind treatment

Participants

Enalapril 20 mg: n=72(44 males,28 females); mean age=53.1(11.0) years; baseline supine SBP=153.8(13.8) mm Hg, DBP=100.4(4.2) mm Hg;
Placebo: n=76(49 males,27 females); mean age=55.6(9.6) years; baseline supine SBP=154.8(11.8) mm Hg, DBP=100.4(4.5) mm Hg

Interventions

Enalapril 20 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SE of change reported; endpoint BP and SD not reported; calculated SD of change from N and SE of change; change in BP data from Figures 1 and 2, p. 235; SE of change data from Table 2, p. 234; Jadad score=3; funding source= Boehringer Ingelheim Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Smith 2000

Methods

Minimum 7‐day washout; 4‐week single‐blind placebo run‐in; inclusion criteria= supine DBP 100‐114 mm Hg during final 2 weeks of run‐in, mean supine DBP could not vary by more than 7 mm Hg between weeks 2 and 3 or weeks 3 and 4 of run‐in, or by more than 10 mm Hg between weeks 2 and 4 of run‐in; 4‐week double‐blind treatment

Participants

Enalapril 20 mg: n=42(31 males,11 females); mean age=52.0 years; baseline supine SBP=155.3 mm Hg, DBP=103.3 mm Hg, HR=72.7 bpm;
Placebo: n=43(24 males,19 females); mean age=52.0 years; baseline supine SBP=159.5 mm Hg, DBP=104.9 mm Hg, HR=72.5 bpm

Interventions

Enalapril 20 mg once daily;
Placebo;
taken with water (120 mL) between 6 AM and 9 AM and at least 1 h before breakfast

Outcomes

Mean change from baseline in trough standing SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough standing HR;
Mean change from baseline in trough supine HR;
WDAE

Notes

BP change and SE of change reported; endpoint BP and SD not reported; calculated SD of change from N and SE of change; change in BP data from Table II, p. 1385; Jadad score=4; funding source= Boehringer Ingelheim Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate
Trevisan 1995

Methods

No minimal BP inclusion criteria; 24‐week total double‐blind treatment, report BP at week 4 of double‐blind treatment

Participants

All patients (normotensive and hypertensive) with non‐insulin‐dependent diabetes mellitus:
Ramipril 1.25 mg: n=60(44 males,16 females); mean age=56(7) years; baseline SBP=147(15) mm Hg, DBP=90(6) mm Hg;
Placebo: n=62(50 males,12 females); mean age=58(7) years; baseline SBP=151(14) mm Hg, DBP=91(6) mm Hg;
Subgroup of patients with BP >/= 160/95 mm Hg:
Ramipril 1.25 mg: n=19; baseline SBP=156(12) mm Hg, DBP=95(4) mm Hg;
Placebo: n=24; baseline SBP=161(9) mm Hg, DBP=95(3) mm Hg

Interventions

Ramipil 1.25 mg once daily;
Placebo

Outcomes

Mean change from baseline in sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Used week 4 BP data only; no minimal BP inclusion criteria, trial included both hypertensive and non‐hypertensive patients; Used BP data from subgroup with BP >/= 160/95 mm Hg; BP change and SD of change not reported; endpoint BP and SD reported; imputed endpoint SD of change; BP data from Table 5, p. 881; time of BP measurement not reported; Jadad score=4; funding source= Hoechst

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Uusitupa 1996

Methods

4‐week normal sodium, placebo run‐in (week 0‐4); inclusion criteria= mean supine DBP 95‐114 mm Hg and mean daytime ambulatory DBP 90‐105 mm Hg after run‐in; 8‐week low‐sodium placebo period (week 4‐12); 12‐week double‐blind treatment (week 12‐24)

Participants

Cilazapril 2.5 mg: n=19(10 males,9 females); mean age=53.7(5.7) years; baseline sitting SBP=157.3(17.1) mm Hg, DBP=104.0(8.0) mm Hg, HR=70(13) bpm;
Placebo: n=20(14 males,6 females); mean age=50.5(9.5) years; baseline sitting SBP=147.0(10.3) mm Hg, DBP=99.4(5.3) mm Hg, HR=70(10) bpm

Interventions

Cilazapril 2.5 mg once daily;
Placebo;
taken before breakfast in the morning between 7 AM and 9 AM

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
Trough sitting HR

Notes

BP change reported; SD of change not reported; 95% confidence interval of change reported; calculated SD of change from 95% CI of change; endpoint BP and SD reported; BP change data from Table 6, p. 323; endpoint BP data from Table 4, p. 322; Jadad score=3; funding source= Hoffmann‐La Roche Ltd.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
VA Study Group 1984

Methods

2‐ to 5‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 92‐109 mm Hg on 2 consecutive clinic visits during run‐in; 7‐week double‐blind treatment

Participants

Captopril 12.5 mg TID: n=83(all males); mean age=55.7(9.8) years; baseline sitting SBP=147.8(14.6) mm Hg, DBP=97.0(3.6) mm Hg;
Captopril 25 mg TID: n=84(all males); mean age=55.7(8.1) years; baseline sitting SBP=147.4(11.9) mm Hg, DBP=97.9(3.7) mm Hg;
Captopril 37.5 mg BID: n=88(all males); mean age=54.9(7.9) years; baseline sitting SBP=149.0(13.1) mm Hg, DBP=97.5(4.7) mm Hg;
Captopril 50 mg TID: n=89(all males); mean age=55.1(8.0) years; baseline sitting SBP=148.2(16.0) mm Hg, DBP=98.1(4.7) mm Hg;
Placebo: n=83(all males); mean age=54.4(8.0) years; baseline sitting SBP=146.3(14.6) mm Hg, DBP=97.8(4.6) mm Hg

Interventions

Captopril 12.5 mg three times daily,
Captopril 25 mg three times daily,
Captopril 37.5 mg twice daily,
Captopril 50 mg three times daily,
Placebo;
all patients were directed to take the capsules at least 1 h before breakfast, 2 h after lunch, and at bedtime, ie, at least 2 h after dinner

Outcomes

Mean change from baseline in sitting SBP/DBP using mercury sphygmomanometer; WDAE; visits were scheduled approx 3 h from the time the patient took his last dose of medication

Notes

BP change and SE of change reported; endpoint BP and SD reported; calculated SD of change from N and change SE; BP data from Table 4, p. 1953; Jadad score=4; funding source= E.R. Squibb & Sons Inc.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate
Vandenburg 1994

Methods

2‐week placebo run‐in; inclusion criteria= sitting DBP 95‐115 mm Hg; 4‐week double‐blind treatment

Participants

Imidapril 5 mg: n=33(21 males,12 females); mean age=53.2(12.1) years; baseline sitting DBP=102.3(5.7) mm Hg;
Imidapril 10 mg: n=31(18 males,13 females); mean age=52.3(11.7) years; baseline sitting DBP=100.8(4.5) mm Hg;
Imidapril 20 mg: n=31(16 males,15 females); mean age=52.5(10.0) years; baseline sitting DBP=101.0(5.6) mm Hg;
Imidapril 40 mg: n=32(21 males,11 females); mean age=49.8(13.6) years; baseline sitting DBP=102.2(5.1) mm Hg;
Placebo: n=35(20 males,15 females); mean age=51.9(11.8) years; baseline sitting DBP=101.3(5.3) mm Hg

Interventions

Imidapril 5 mg once daily;
Imidapril 10 mg once daily;
Imidapril 20 mg once daily;
Imidapril 40 mg once daily;
Placebo

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
Trough standing SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change reported; endpoint BP and SD reported; change in BP data from Table 4, p. 271; Jadad score=3; funding source= Tanabe Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Vaur 1998

Methods

2‐week washout; 2‐week single‐blind placebo run‐in; inclusion criteria= mean supine DBP 95‐114 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

Trandolapril 2 mg: n=24(15 males,9 females); mean age=56(10) years; baseline sitting SBP=163(16) mm Hg, DBP=101(6) mm Hg;
Placebo: n=10(5 males,5 females); mean age=53(12) years; baseline SBP=157(14) mm Hg, DBP=100(7) mm Hg

Interventions

Trandolapril 2 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer

Notes

BP change and SD of change reported; endpoint BP and SD not reported; SBP/DBP data from Table 3, p. 110; Jadad score=3; funding source= Roussel Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Villamil 1987

Methods

2‐week placebo run‐in; inclusion criteria= supine and standing DBP 95‐120 mm Hg after run‐in; 4‐week double‐blind treatment

Participants

Ramipril 2.5 mg: n=28(12 males,16 females); median age=54 years; baseline SBP=162.0 mm Hg, DBP=101.1 mm Hg;
Ramipril 5 mg: n=29(11 males,18 females); median age=53 years; baseline SBP=166.8 mm Hg, DBP=103.2 mm Hg;
Placebo: n=27(15 males,12 females); median age=52 years; baseline SBP=166.6 mm Hg, DBP=101.5 mm Hg

Interventions

Ramipril 2.5 mg once daily;
Ramipril 5 mg once daily;
Placebo;
administered between 6 AM and 8 AM

Outcomes

Mean change from baseline in trough standing SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SEM of change reported, endpoint BP and SD not reported; calculated SD of change from N and change SE; BP data from Tables III and IV, p. 112D; Jadad score=3; funding source= Hoechst AG

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Waeber 1999

Methods

4‐week placebo run‐in; inclusion criteria= sitting DBP 95‐110 mm Hg after run‐in; 12‐week total double‐blind treatment, titrated to response at 4 weeks

Participants

Enalapril 10 mg: n=321(188 males,133 females); mean age=52.4(10.2) years; baseline sitting SBP=158.0(15.4) mm Hg, DBP=100.9(4.6) mm Hg;
Placebo: n=304(165 males,135 females); mean age=51.0(10.7) years; baseline SBP=157.2(15.3) mm Hg, DBP=101.0(4.4) mm Hg

Interventions

Enalapril 10 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Used week 4 BP data only; BP change and SD of change reported, endpoint BP and SD not reported; BP data from Figure I, p. 917; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Weinberger 1990

Methods

2‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg, inclusive, on 2 consecutive visits (weeks 2 and 4 of run‐in) with </= 10mm Hg difference between 2 visits; 4‐week double‐blind treatment

Participants

Benazepril 5 mg: n=38(23 males,15 females); mean age=51.1 years; baseline sitting SBP=152.7(15.2) mm Hg, DBP=101.2(5.3) mm Hg;
Benazepril 10 mg: n=34(23 males,11 females); mean age=51.9 years; baseline sitting SBP=153.1(13.7) mm Hg, DBP=101.8(5.7) mm Hg;
Benazepril 20 mg: n=36(23 males,13 females); mean age=50.4 years; baseline sitting SBP=151.9(15.7) mm Hg, DBP=101.7(4.7) mm Hg;
Benazepril 40 mg: n=34(24 males,10 females); mean age=50.4 years; baseline sitting SBP=151.6(15.9) mm Hg, DBP=102.1(5.6) mm Hg;
Placebo: n=31(21 males,10 females); mean age=48.2 years; baseline sitting SBP=150.7(14.3) mm Hg, DBP=101.7(4.9) mm Hg

Interventions

Benazepril 5 mg once daily;
Benazepril 10 mg once daily;
Benazepril 20 mg once daily;
Benazepril 40 mg once daily;
Placebo

Outcomes

Trough sitting DBP using mercury sphygmomanometer;
Mean change from baseline in peak sitting DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SE of change reported, endpoint BP reported, endpoint SE not reported; calculated SD of change from N and SE of change; DBP data from Table III, p. 325; Jadad score=2; funding source= Ciba‐Geigy

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Weir 1995

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= mean supine DBP 95‐114 mm Hg during both of final 2 consecutive weeks of run‐in; 6‐week double‐blind treatment

Participants

Black and white patients reported in Weir 1995:
Trandolapril 1 mg: n=51(33 males,18 females); mean age=58.3(11.4) years; baseline sitting SBP=154.8(15.0) mm Hg, DBP=100.3(4.3) mm Hg;
Trandolapril 2 mg: n=53(36 males,17 females); mean age=57.3(10.9) years; baseline sitting SBP=151.9(13.1) mm Hg, DBP=101.7(5.1) mm Hg;
Trandolapril 4 mg: n=53(28 males,25 females); mean age=53.0(12.4) years; baseline sitting SBP=147.6(13.8) mm Hg, DBP=99.9(4.4) mm Hg;
Placebo: n=50(35 males,15 females); mean age=60.6(9.9) years; baseline SBP=152.1(14.9) mm Hg, DBP=100.9(5.0) mm Hg
Only black patients reported in Weir 1998 (duplicate publication):
Trandolapril 0.25 mg: n=23(12 males,11 females); mean age=48.6(12.7) years; baseline supine SBP=159.1(13.5) mm Hg, DBP=101.7(5.3) mm Hg;
Trandolapril 0.5 mg: n=22(9 males,13 females); mean age=49.4(12.3) years; baseline supine SBP=152.1(11.7) mm Hg, DBP=101.6(4.9) mm Hg;
Trandolapril 1 mg: n=23(7 males,16 females); mean age=52.7(11.1) years; baseline supine SBP=150.7(13.1) mm Hg, DBP=99.7(3.5) mm Hg (same patients as Weir 1995);
Trandolapril 2 mg: n=22(10 males,12 females); mean age=53.0(10.2) years; baseline supine SBP=146.1(11.4) mm Hg, DBP=99.1(3.2) mm Hg (same patients as Weir 1995);
Trandolapril 4 mg: n=60(28 males,32 females); mean age=53.6(10.8) years; baseline supine SBP=156.2(16.1) mm Hg, DBP=101.7(4.9) mm Hg (same patients as Weir 1995);
Trandolapril 8 mg: n=38(19 males,19 females); mean age=55.3(11.9) years; baseline supine SBP=158.7(19.3) mm Hg, DBP=101.4(4.3) mm Hg;
Trandolapril 12 mg: n=38(19 males,19 females); mean age=53.1(13.5) years; baseline supine SBP=153.0(12.4) mm Hg, DBP=100.9(4.1) mm Hg;
Trandolapril 16 mg: n=36(15 males,21 females); mean age=54.4(12.2) years; baseline supine SBP=159.5(17.3) mm Hg, DBP=100.5(3.7) mm Hg;
Placebo: n=60(27 males,33 females); mean age=53.5(10.0) years; baseline supine SBP=155.7(15.5) mm Hg, DBP=100.6(4.2) mm Hg

Interventions

Trandolapril 0.25 mg once daily (black patients only);
Trandolapril 0.5 mg once daily (black patients only);
Trandolapril 1 mg once daily (black and white patients);
Trandolapril 2 mg once daily (black and white patients);
Trandolapril 4 mg once daily (black and white patients);
Trandolapril 8 mg once daily (black patients only);
Trandolapril 12 mg once daily (black patients only);
Trandolapril 16 mg once daily (black patients only);
Placebo;
administered between 8 AM and 10 AM

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer (Trandolapril 1, 2, 4 mg treatment arms);
Mean change from baseline in trough supine SBP/DBP using mercury sphygmomanometer (Trandolapril 0.25, 0.5, 8, 12, 16 mg treatment arms);
WDAE

Notes

Weir 1995: BP change and SE of change reported; calculated SD of change from N and SE of change; endpoint BP and SD not reported; SBP/DBP data from Table 2, p. 126; Jadad score=3; funding source= Knoll Pharma

Weir 1998: BP change and SE of change reported for trandalopril groups; SBP SE of change in placebo group not reported; DBP SE of change in placebo group reported; imputed baseline SBP SE for SE of change; calculated SD of change from N and SE of change; endpoint BP and SD not reported; SBP/DBP data from Table 2, p. 191

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Whalen 1989

Methods

2‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg after run‐in; 8‐week double‐blind treatment

Participants

All patients: n=165;
Benazepril 20 mg: n=50; baseline sitting SBP=156 mmHg, DBP=103 mm Hg;
Benazepril 40 mg: n=50; baseline sitting SBP=154 mmHg, DBP=102 mm Hg;
Benazepril 80 mg: n=37; baseline sitting SBP=161 mmHg, DBP=104 mm Hg;
Placebo: n=50; baseline sitting SBP=154 mmHg, DBP=103 mm Hg

Interventions

Benazepril 20 mg once daily;
Benazepril 40 mg once daily;
Benazepril 80 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough sitting SBP/DBP;
Mean change from baseline in peak sitting SBP/DBP

Notes

BP change reported; SD of change not reported, endpoint BP and SD not reported; imputed overall trial mean SD of change; BP data from abstract; BP measurement device not reported; Jadad score=2; funding source= Ciba‐Geigy Inc.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Whelton 1992

Methods

2‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg during run‐in; 4‐week double‐blind treatment

Participants

Enalapril 10 mg: n=36(24 males,12 females); mean age=53 years; baseline sitting SBP=152.9 mm Hg, DBP=100.5 mm Hg;
Lisinopril 10 mg: n=37(22 males,15 females); mean age=51 years; baseline sitting SBP=146.9 mm Hg, DBP=99.1 mm Hg;
Placebo: n=37(23 males,14 females); mean age=50 years; baseline sitting SBP=149.9 mm Hg, DBP=99.5 mm Hg

Interventions

Enalapril 10 mg once daily;
Lisinopril 10 mg once daily;
Placebo;
administered between 8 AM and 9 AM

Outcomes

Baseline adjusted mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SE of change reported, endpoint BP and SD not reported; calculated SD of change from N and change SE; BP data from Table II, p. 328; Jadad score=3; funding source= ICI Americas Inc.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
White 1988

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= DBP 95‐114 mm Hg after run‐in; 4‐week double‐bind treatment at fixed dose; after 4 weeks (week 0‐4), patients with inadequate BP response had their doses doubled during the second 4 weeks (week 4‐8); hydrochlorothiazide 12.5 mg (in a single morning dose) was added during final 4 weeks (week 8‐12)

Participants

All patients: n=18(10 males,8 females); mean age=52(12) years;
Cilazapril 2.5 mg: n=9; baseline sitting SBP=155(15) mm Hg, DBP=104(4) mm Hg, HR=77(8) bpm;
Placebo: n=9; baseline sitting SBP=152(15) mm Hg, DBP=100(4) mm Hg, HR=83(8) bpm

Interventions

Cilazapril 2.5 mg once daily;
Placebo

Outcomes

Trough sitting SBP/DBP using mercury sphygmomanometer;
Trough standing SBP/DBP using mercury sphygmomanometer;
Trough sitting HR;
Trough standing HR;
WDAE

Notes

Used week 4 BP data only; BP change and SD of change not reported; endpoint BP and SD reported; imputed endpoint SD for SD of change; BP data from Table 1, p. 174; Jadad score=3; funding source= Hoffmann‐La Roche Ltd.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
White 1995

Methods

Minimum 1‐week washout; 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg on 2 separate visits at end of placebo run‐in, with difference between visits of 10 mm Hg or less; 8‐week double‐blind treatment

Participants

Moexipril 7.5 mg: n=16(12 males,4 females); mean age=56(12) years; baseline sitting SBP=161(12) mm Hg, DBP=103(4) mm Hg, HR=76(8) bpm;
Moexipril 15 mg: n=18(16 males,2 females); mean age=58(9) years; baseline sitting SBP=157(13) mm Hg, DBP=104(4) mm Hg, HR=78(13) bpm;
Placebo: n=17(15 males,2 females); mean age=50(12) years; baseline sitting SBP=149(17) mm Hg, DBP=106(4) mm Hg, HR=77(8) bpm

Interventions

Moexipril 7.5 mg once daily;
Moexipril 15 mg once daily;
Placebo

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
Mean change from baseline in trough sitting HR

Notes

BP change and SD of change reported, endpoint BP and SD not reported; change in BP data from Table II, p. 235; Jadad score=2; funding source= Schwarz Pharma

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
White 2002

Methods

1‐ to 2‐week washout period for patients who were currently receiving antihypertensive therapy; 2‐ to 4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐115 mm Hg during 2 consecutive weeks of run‐in; also required that ambulatory awake DBP >/= 85 mm Hg; total 8‐week double‐blind treatment: 4‐week low‐dose treatment (week 0‐4), forced titration at week 4 to high‐dose, 4‐week high‐dose treatment (week 4‐8)

Participants

Enalapril 10 mg: n=99(58 males,41 females); mean age=54(10) years; baseline SBP=145(16) mm Hg, DBP=93(8) mm Hg; baseline HR=72(10) bpm;
Placebo: n=46(30 males,16 females); mean age=56(11) years; baseline SBP=148(12) mm Hg, DBP=95(6) mm Hg; baseline HR=71(9) bpm

Interventions

Enalapril 10 mg once daily;
Placebo;
administered in the morning

Outcomes

Mean change from baseline in trough sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

Used week 4 BP data only; BP change and SD of change reported, endpoint BP and SD not reported; BP data from Table IV, p. 663; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Yebes 1993

Methods

4‐week single‐blind placebo washout; inclusion criteria= sitting DBP > 100 and < 115 mm Hg after washout; 8‐week double‐blind treatment, randomized to either placebo or quinapril 20 mg once daily for 4 weeks with optional titration to 40 mg once daily for subsequent 4 weeks based on diastolic response

Participants

Quinapril: n=10; mean age=55(14.9) years; baseline SBP=161(22.2) mm Hg, DBP=105(5.6) mm Hg;
Placebo: n=11; mean age=50(9.9) years; baseline SBP=154(20.6) mm Hg, DBP=103(5.0) mm Hg

Interventions

Quinapril 20 mg once daily;
Placebo

Outcomes

Mean change from baseline in sitting SBP/DBP

Notes

Used week 4 BP data only; BP change and SD of change reported, endpoint BP and SD reported; time of dosing not reported; time of BP measurement not reported; SBP data from Table IA, p. 321, DBP data from Table IIA, p. 323; time of BP measurement not reported; BP measurement device not reported; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Yodfat 1993

Methods

4‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP > 100 mm Hg after run‐in; 8‐week double‐blind treatment

Participants

Cilazapril: n=94(67 males,27 females); mean age=52.4(8.1) years; baseline BP not reported;
Placebo: n=46(28 males,18 females); mean age=54.1(7.0) years; baseline BP not reported

Interventions

Cilazapril 2.5 mg once daily;
Cilazapril 5 mg once daily;
Placebo;
taken at approximately 12 PM before meal

Outcomes

Mean change from baseline in trough sitting DBP using mercury sphygmomanometer;
WDAE

Notes

SBP change not reported; DBP change reported; SD of change not reported, endpoint SBP/DBP and SD not reported; imputed overall trial mean SD of change for DBP; baseline BP not reported; BP data from Figure 1, p. 119; Jadad score=3; funding source= not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Zamboulis 1996

Methods

4‐week washout; 2‐week single‐blind placebo run‐in; inclusion criteria= sitting DBP 95‐114 mm Hg at end of placebo run‐in; 4‐week double‐blind treatment

Participants

Fosinopril 20 mg: n=12(8 males,4 females); mean age=51 years; baseline seated SBP=150.8(15.9) mm Hg, DBP=108.8(4.7) mm Hg; baseline HR=76.9(5.3) bpm;
Placebo: n=11(7 males,4 females); mean age=45 years; baseline seated SBP=143.0(20.0) mm Hg, DBP=95.5(12.6) mm Hg; baseline HR=79.0(9.8) bpm

Interventions

Fosinopril 20 mg once daily;
Placebo

Outcomes

Sitting SBP/DBP using mercury sphygmomanometer;
WDAE

Notes

BP change and SD of change not reported, endpoint BP and SD reported; imputed endpoint SD for SD of change; time of BP measurement (peak and/or trough) not reported; BP data from Table 1, p. 254; Jadad score=3; funding source= Bristol‐Myers Squibb

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

BP=blood pressure, DBP=diastolic blood pressure; SBP=systolic blood pressure; SD=standard deviation; WDAE=withdrawal due to adverse effects; bpm=beats per minute

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Bainbridge 1993

Crossover trial with no pre‐crossover data for first 4 weeks of treatment (ramipril 2.5 mg/day vs. placebo).

Bakris 2002

Parallel group trial with 8‐week treatment period, forced titration at 4 weeks. Pre‐titration data not reported (enalapril 10 mg/day vs. losartan 50 mg/day vs. placebo).

Beaulieu 1993

Crossover trial with no pre‐crossover data for first 4 weeks of treatment (fosinopril 20 mg/day vs. placebo).

Bergstrand 1985

Balanced, two‐period, incomplete‐block design with 2 treatment periods of 3‐weeks duration. First treatment period data not reported (enalapril 2.5, 5, 10, 20, 40 vs. placebo).

Bohlen 1996

Parallel group trial with 6‐week treatment period, titration in non‐responders at 4 weeks. Pre‐titration data not reported (perindopril 4 mg/day vs. placebo).

Canter 1994

Parallel group trial with 8‐week treatment period. Number of patients per treatment arm not reported (quinapril 2.5, 10, 40 mg/day vs. placebo).

Canter 1994a

Crossover trial with no pre‐crossover data for first 4 weeks of treatment (quniapril 20 mg/day vs. placebo).

Cleroux 1994

Crossover trial with no pre‐crossover data for first 4 weeks of treatment. 8‐week treatment periods but titration in non‐responders after 4 weeks treatment (quinapril 10 mg/day vs. placebo).

Cuspidi 1997

Crossover trial with no pre‐crossover data for first 4 weeks of treatment (lisinopril 20 mg/day vs. placebo).

Duprez 1986

Crossover trial with no pre‐crossover data for first 6 weeks of treatment (enalapril 20 mg/day vs. placebo).

Fagard 2001

Crossover trial with no pre‐crossover data reported for first 6 weeks of treatment (enalapril 20 mg/day vs. losartan 50 mg/day vs. placebo).

Gall 1992

Crossover trial with no pre‐crossover data for first 4 weeks of treatment. 8‐week treatment periods but titration in non‐responders after 4 weeks treatment (captopril 50 mg/day vs. placebo).

Gans 1993

Parallel group trial with 8‐week treatment period, titration in non‐responders at 4 weeks. Pre‐titration data not reported (cilazapril 2.5 mg/day vs. placebo).

Gleerup 1996

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (spirapril 6 mg/day vs. placebo).

Guitard 1994a

Crossover trial with no pre‐crossover data reported for first 3 weeks of treatment (spirapril 3, 6, 12, 24 mg/day vs. placebo).

Gupta 1990

Crossover trial with no pre‐crossover data for first 4 weeks of treatment (quinapril 40 mg/day vs. placebo).

Homuth 1993a

Parallel group trial with 6‐week treatment period. BP data not extractable from figures (ramipril 2.5, 10, 20 mg/day vs. placebo).

Hu 1999

Parallel group trial with 12‐week treatment period, titration in non‐responders every 4 weeks. Pre‐titration data not reported (captopril 50 mg/day vs. placebo).

Kahan 1999

Crossover trial with no pre‐crossover data reported for first 6 weeks of treatment (ramipril 5 mg/day vs. placebo).

Karlberg 1987

Parallel group trial with 4‐week treatment period. BP data for placebo group not reported at week 4 (ramipril 5 mg/day vs. ramipril 10 mg/day vs. placebo).

Kjeldsen 1992

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (quinapril 40 mg/day vs. placebo).

Lacourciere 1999

Parallel group trial with 8‐week treatment period. BP data for placebo group not reported (lisinopril 20 mg/day vs. telmisartan 80 mg/day vs. placebo).

Lavezzaro 1990

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (captopril 100 mg/day vs. placebo).

Leonetti 1991

Parallel group trial with 8‐week treatment period, titration in non‐responders at 4 weeks. Pre‐titration data not reported (captopril 50 mg/day vs. placebo).

Littler 1990

Crossover trial with no pre‐crossover data reported for first 6 weeks of treatment (perindopril 8 mg/day vs. placebo).

Louis 1992

Parallel group trial with 4‐week treatment period. Only maximum BP reduction is reported (perindopril 2, 4, 8 mg/day vs. placebo).

Miyajima 1999

Parallel group trial with 12‐week treatment period, titration in non‐responders at 4 weeks. Pre‐titration data not reported (imidapril 5 mg/day vs. placebo).

Morgan 2001

Crossover trial with no pre‐crossover data for first 4 weeks of treatment. 8‐week treatment periods but titration in non‐responders after 4 weeks treatment (enalapril 20 mg/day vs. perindopril 4 mg/day vs. placebo).

Petersen 1996

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (spirapril 24 mg/day vs. placebo).

Petrie 2000

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (trandolapril 2 mg/day vs. placebo).

Petrov 2001

Crossover trial with no pre‐crossover data reported for first 6 weeks of treatment (enalapril 20 mg/day vs. losartan 50 mg/day vs. placebo).

Plouin 1991

Parallel group trial with 8‐week treatment period, titration in non‐responders at 4 weeks. Pre‐titration data not reported (perindopril 4 mg/day vs. placebo).

Pritchard 1996

Crossover trial with no pre‐crossover data reported for first 3 weeks of treatment (trandolapril 2 mg/day vs. placebo).

Reisin 1997

Parallel group trial with 12‐week treatment period, titration in non‐responders every 4 weeks. Pre‐titration data not reported (lisinopril 10 mg/day vs. placebo).

Salvetti 1987

Crossover trial with no baseline data and no pre‐crossover data reported for first 4 weeks of captopril 100 mg/day vs. placebo. Only mean arterial blood pressure values given.

Salvetti 1988

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (captopril 50, 100 mg/day vs. placebo).

Salvetti 1989

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (enalapril 10, 20, 40 mg/day vs. placebo).

Samuelsson 1992

Parallel group trial with 8‐week treatment period, titration in non‐responders at 2 or 4 weeks. Pre‐titration data not reported (lisinopril 20 mg/day vs. placebo).

Sassano 1984a

Parallel group trial with 6‐month treatment period. Additional BP lowering drugs added to enalapril 20 mg in non‐responders at 4 weeks. Data during first 4 weeks not reported.

Scholze 1993

Parallel group trial with 6‐week treatment period. Number of patients per treatment arm not reported (ramipril 2.5, 5, 10 mg/day vs. placebo).

Thurig 1995

Crossover trial with no pre‐crossover data reported for first 8 weeks of treatment (lisinopril 20 mg/day vs. placebo).

Tomei 1992

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (lisinopril 20 mg/day vs. placebo).

Wiggam 1998

Crossover trial with no pre‐crossover data reported for first 8 weeks of treatment (captopril 100 mg/day vs. placebo).

Wilkins 1983

Parallel group trial with 12‐week treatment period, titration in non‐responders every 4 weeks. Pre‐titration data not reported (enalapril 10 mg/day vs. placebo).

Wing 1987

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (enalapril 20 mg/day vs. placebo).

Wing 1988

Crossover trial with no pre‐crossover data reported for first 4 weeks of treatment (enalapril 20 mg/day vs. placebo).

Youssef 1993

Parallel group trial with 8‐week treatment. Highly suspicious data (enalapril 20 mg/day vs. benazepril 10 mg/day vs. placebo).

Zanchetti 2001

Parallel group trial with 8‐week treatment period, titration in non‐responders at 4 weeks. Pre‐titration data not reported (enalapril 10 mg/day vs. candesartan 4 mg/day vs. placebo).

Data and analyses

Open in table viewer
Comparison 1. Benazepril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

7

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.1
Comparison 1 Benazepril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 1 Benazepril vs Placebo, Outcome 1 Change in trough SBP.

1.1 2 mg

1

36

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐11.87, 12.27]

1.2 4 mg

1

71

Mean Difference (IV, Fixed, 95% CI)

‐5.5 [‐12.17, 1.17]

1.3 5 mg

2

60

Mean Difference (IV, Fixed, 95% CI)

‐6.52 [‐16.09, 3.06]

1.4 10 mg

3

284

Mean Difference (IV, Fixed, 95% CI)

‐2.68 [‐5.98, 0.61]

1.5 20 mg

6

422

Mean Difference (IV, Fixed, 95% CI)

‐8.30 [‐11.14, ‐5.46]

1.6 40 mg (Max Dose)

2

74

Mean Difference (IV, Fixed, 95% CI)

‐8.68 [‐14.00, ‐1.35]

1.7 80 mg

1

50

Mean Difference (IV, Fixed, 95% CI)

‐11.40 [‐19.95, ‐2.85]

2 Change in trough DBP Show forest plot

7

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 1.2
Comparison 1 Benazepril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 1 Benazepril vs Placebo, Outcome 2 Change in trough DBP.

2.1 2 mg

1

36

Mean Difference (IV, Fixed, 95% CI)

1.1 [‐6.54, 8.74]

2.2 4 mg

1

71

Mean Difference (IV, Fixed, 95% CI)

‐4.10 [‐7.95, ‐0.25]

2.3 5 mg

2

60

Mean Difference (IV, Fixed, 95% CI)

‐2.04 [‐8.60, 4.53]

2.4 10 mg

3

283

Mean Difference (IV, Fixed, 95% CI)

‐0.72 [‐2.67, 1.22]

2.5 20 mg

6

422

Mean Difference (IV, Fixed, 95% CI)

‐4.53 [‐6.14, ‐2.93]

2.6 40 mg (Max Dose)

2

74

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐9.15, ‐0.31]

2.7 80 mg

1

51

Mean Difference (IV, Fixed, 95% CI)

‐6.80 [‐11.60, 0.00]
Open in table viewer
Comparison 2. Captopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in SBP Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 2.1
Comparison 2 Captopril vs Placebo, Outcome 1 Change in SBP.

Comparison 2 Captopril vs Placebo, Outcome 1 Change in SBP.

1.1 37.5 mg

1

111

Mean Difference (IV, Fixed, 95% CI)

‐8.6 [‐14.95, ‐2.25]

1.2 50 mg

3

324

Mean Difference (IV, Fixed, 95% CI)

‐8.25 [‐11.34, ‐5.16]

1.3 75 mg

2

124

Mean Difference (IV, Fixed, 95% CI)

‐9.16 [‐15.09, ‐3.23]

1.4 100 mg

1

96

Mean Difference (IV, Fixed, 95% CI)

‐12.0 [‐18.17, ‐5.83]

1.5 150 mg (Max Dose)

1

117

Mean Difference (IV, Fixed, 95% CI)

‐12.0 [‐18.06, ‐5.94]

1.6 200 mg

1

94

Mean Difference (IV, Fixed, 95% CI)

‐12.20 [‐18.32, ‐6.08]

2 Change in DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 2.2
Comparison 2 Captopril vs Placebo, Outcome 2 Change in DBP.

Comparison 2 Captopril vs Placebo, Outcome 2 Change in DBP.

2.1 37.5 mg

1

111

Mean Difference (IV, Fixed, 95% CI)

‐5.40 [‐8.74, ‐2.06]

2.2 50 mg

4

500

Mean Difference (IV, Fixed, 95% CI)

‐4.58 [‐6.02, ‐3.15]

2.3 75 mg

2

124

Mean Difference (IV, Fixed, 95% CI)

‐5.92 [‐9.16, ‐2.68]

2.4 100 mg

1

97

Mean Difference (IV, Fixed, 95% CI)

‐6.4 [‐9.91, ‐2.89]

2.5 150 mg (Max Dose)

1

117

Mean Difference (IV, Fixed, 95% CI)

‐7.3 [‐10.43, ‐4.17]

2.6 200 mg

1

94

Mean Difference (IV, Fixed, 95% CI)

‐6.70 [‐10.23, ‐3.17]
Open in table viewer
Comparison 3. Cilazapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

9

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 3.1
Comparison 3 Cilazapril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 3 Cilazapril vs Placebo, Outcome 1 Change in trough SBP.

1.1 2.5 mg

9

361

Mean Difference (IV, Fixed, 95% CI)

‐5.16 [‐8.32, 0.00]

1.2 5 mg

5

277

Mean Difference (IV, Fixed, 95% CI)

‐5.75 [‐9.38, ‐2.12]

1.3 10 mg (Max Dose)

1

67

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐14.07, 0.07]

2 Change in trough DBP Show forest plot

14

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 3.2
Comparison 3 Cilazapril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 3 Cilazapril vs Placebo, Outcome 2 Change in trough DBP.

2.1 0.5 mg

1

129

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐3.45, 2.45]

2.2 1 mg

1

56

Mean Difference (IV, Fixed, 95% CI)

1.1 [‐3.66, 5.86]

2.3 2.5 mg

13

558

Mean Difference (IV, Fixed, 95% CI)

‐3.32 [‐4.70, ‐1.94]

2.4 5 mg

9

569

Mean Difference (IV, Fixed, 95% CI)

‐3.49 [‐4.87, ‐2.11]

2.5 10 mg (Max Dose)

2

190

Mean Difference (IV, Fixed, 95% CI)

‐4.06 [‐6.44, ‐1.67]
Open in table viewer
Comparison 4. Enalapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

17

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 4.1
Comparison 4 Enalapril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 4 Enalapril vs Placebo, Outcome 1 Change in trough SBP.

1.1 5 mg

4

552

Mean Difference (IV, Fixed, 95% CI)

‐5.56 [‐7.95, ‐3.18]

1.2 10 mg

8

1122

Mean Difference (IV, Fixed, 95% CI)

‐5.42 [‐5.00, ‐3.84]

1.3 20 mg

8

911

Mean Difference (IV, Fixed, 95% CI)

‐9.61 [‐11.35, ‐7.86]

2 Change in trough DBP Show forest plot

19

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 4.2
Comparison 4 Enalapril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 4 Enalapril vs Placebo, Outcome 2 Change in trough DBP.

2.1 5 mg

5

702

Mean Difference (IV, Fixed, 95% CI)

‐2.46 [‐3.67, ‐1.25]

2.2 10 mg

8

1122

Mean Difference (IV, Fixed, 95% CI)

‐3.10 [‐3.99, ‐2.20]

2.3 20 mg

9

984

Mean Difference (IV, Fixed, 95% CI)

‐5.34 [‐6.29, ‐4.38]
Open in table viewer
Comparison 5. Fosinopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 5.1
Comparison 5 Fosinopril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 5 Fosinopril vs Placebo, Outcome 1 Change in trough SBP.

1.1 2.5 mg

1

38

Mean Difference (IV, Fixed, 95% CI)

‐2.9 [‐13.01, 7.21]

1.2 5 mg

1

94

Mean Difference (IV, Fixed, 95% CI)

‐3.70 [‐10.37, 2.97]

1.3 10 mg

3

151

Mean Difference (IV, Fixed, 95% CI)

‐3.86 [‐9.03, 1.30]

1.4 20 mg

5

208

Mean Difference (IV, Fixed, 95% CI)

‐9.26 [‐13.72, ‐4.79]

1.5 40 mg (Max Dose)

3

158

Mean Difference (IV, Fixed, 95% CI)

‐7.81 [‐12.91, ‐2.72]

2 Change in trough DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 5.2
Comparison 5 Fosinopril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 5 Fosinopril vs Placebo, Outcome 2 Change in trough DBP.

2.1 2.5 mg

1

39

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐6.31, 4.91]

2.2 5 mg

1

93

Mean Difference (IV, Fixed, 95% CI)

‐3.20 [‐7.12, 0.72]

2.3 10 mg

3

151

Mean Difference (IV, Fixed, 95% CI)

‐3.45 [‐6.42, ‐0.47]

2.4 20 mg

5

209

Mean Difference (IV, Fixed, 95% CI)

‐7.79 [‐10.12, ‐5.46]

2.5 40 mg (Max Dose)

3

157

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐7.69, ‐1.76]
Open in table viewer
Comparison 6. Imidapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 6.1
Comparison 6 Imidapril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 6 Imidapril vs Placebo, Outcome 1 Change in trough SBP.

1.1 5 mg

1

41

Mean Difference (IV, Fixed, 95% CI)

‐4.90 [‐15.96, 6.16]

1.2 10 mg

1

40

Mean Difference (IV, Fixed, 95% CI)

‐8.90 [‐20.02, 2.22]

1.3 20 mg (Max Dose)

1

40

Mean Difference (IV, Fixed, 95% CI)

‐12.90 [‐24.22, ‐1.58]

1.4 40 mg

1

41

Mean Difference (IV, Fixed, 95% CI)

‐10.60 [‐21.36, 0.16]

2 Change in trough DBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 6.2
Comparison 6 Imidapril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 6 Imidapril vs Placebo, Outcome 2 Change in trough DBP.

2.1 5 mg

1

42

Mean Difference (IV, Fixed, 95% CI)

‐3.2 [‐10.28, 3.88]

2.2 10 mg

1

39

Mean Difference (IV, Fixed, 95% CI)

‐7.40 [‐15.16, 0.36]

2.3 20 mg (Max Dose)

1

40

Mean Difference (IV, Fixed, 95% CI)

‐6.3 [‐13.60, 1.00]

2.4 40 mg

1

41

Mean Difference (IV, Fixed, 95% CI)

‐6.50 [‐13.89, 0.89]
Open in table viewer
Comparison 7. Lisinopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 7.1
Comparison 7 Lisinopril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 7 Lisinopril vs Placebo, Outcome 1 Change in trough SBP.

1.1 1.25 mg

1

46

Mean Difference (IV, Fixed, 95% CI)

3.2 [‐5.00, 13.40]

1.2 5 mg

1

47

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐13.22, 9.22]

1.3 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐7.75 [‐9.98, ‐5.51]

1.4 20 mg

1

50

Mean Difference (IV, Fixed, 95% CI)

‐7.80 [‐18.67, 3.07]

1.5 80 mg (Max Dose)

1

50

Mean Difference (IV, Fixed, 95% CI)

‐13.8 [‐24.46, ‐3.14]

2 Change in trough DBP Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 7.2
Comparison 7 Lisinopril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 7 Lisinopril vs Placebo, Outcome 2 Change in trough DBP.

2.1 1.25 mg

1

46

Mean Difference (IV, Fixed, 95% CI)

2.8 [‐2.34, 7.94]

2.2 5 mg

1

47

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐5.32, 5.32]

2.3 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐4.71 [‐5.92, ‐3.50]

2.4 20 mg

1

51

Mean Difference (IV, Fixed, 95% CI)

‐4.6 [‐10.17, 0.97]

2.5 80 mg (Max Dose)

1

49

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐11.72, ‐0.28]
Open in table viewer
Comparison 8. Moexipril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 8.1
Comparison 8 Moexipril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 8 Moexipril vs Placebo, Outcome 1 Change in trough SBP.

1.1 7.5 mg

3

168

Mean Difference (IV, Fixed, 95% CI)

‐1.83 [‐6.71, 3.05]

1.2 15 mg

4

265

Mean Difference (IV, Fixed, 95% CI)

‐8.45 [‐11.99, ‐4.91]

2 Change in trough DBP Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 8.2
Comparison 8 Moexipril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 8 Moexipril vs Placebo, Outcome 2 Change in trough DBP.

2.1 7.5 mg

3

167

Mean Difference (IV, Fixed, 95% CI)

‐2.23 [‐4.63, 0.16]

2.2 15 mg

4

266

Mean Difference (IV, Fixed, 95% CI)

‐4.38 [‐6.29, ‐2.46]
Open in table viewer
Comparison 9. Perindopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 9.1
Comparison 9 Perindopril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 9 Perindopril vs Placebo, Outcome 1 Change in trough SBP.

1.1 2 mg

2

85

Mean Difference (IV, Fixed, 95% CI)

‐3.24 [‐13.20, 6.72]

1.2 4 mg

6

820

Mean Difference (IV, Fixed, 95% CI)

‐6.76 [‐9.41, ‐4.12]

1.3 8 mg (Max Dose)

2

82

Mean Difference (IV, Fixed, 95% CI)

‐9.81 [‐19.32, ‐0.31]

1.4 16 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐8.9 [‐19.65, 1.85]

2 Change in trough DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 9.2
Comparison 9 Perindopril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 9 Perindopril vs Placebo, Outcome 2 Change in trough DBP.

2.1 2 mg

2

85

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐6.40, 2.20]

2.2 4 mg

6

820

Mean Difference (IV, Fixed, 95% CI)

‐4.91 [‐6.21, ‐3.61]

2.3 8 mg (Max Dose)

2

82

Mean Difference (IV, Fixed, 95% CI)

‐5.81 [‐10.11, ‐1.52]

2.4 16 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐5.50 [‐10.09, ‐0.91]
Open in table viewer
Comparison 10. Quinapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 10.1
Comparison 10 Quinapril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 10 Quinapril vs Placebo, Outcome 1 Change in trough SBP.

1.1 20 mg

3

196

Mean Difference (IV, Fixed, 95% CI)

‐5.87 [‐9.75, ‐1.99]

2 Change in trough DBP Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 10.2
Comparison 10 Quinapril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 10 Quinapril vs Placebo, Outcome 2 Change in trough DBP.

2.1 20 mg

3

196

Mean Difference (IV, Fixed, 95% CI)

‐3.26 [‐5.85, ‐0.68]
Open in table viewer
Comparison 11. Ramipril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 11.1
Comparison 11 Ramipril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 11 Ramipril vs Placebo, Outcome 1 Change in trough SBP.

1.1 1.25 mg

2

98

Mean Difference (IV, Fixed, 95% CI)

4.06 [‐1.97, 10.08]

1.2 2.5 mg

4

197

Mean Difference (IV, Fixed, 95% CI)

‐4.38 [‐9.71, 0.95]

1.3 5 mg

4

195

Mean Difference (IV, Fixed, 95% CI)

‐7.47 [‐12.76, ‐2.19]

1.4 10 mg

4

257

Mean Difference (IV, Fixed, 95% CI)

‐5.74 [‐9.33, ‐2.16]

2 Change in trough DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 11.2
Comparison 11 Ramipril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 11 Ramipril vs Placebo, Outcome 2 Change in trough DBP.

2.1 1.25 mg

2

97

Mean Difference (IV, Fixed, 95% CI)

1.78 [‐1.83, 5.39]

2.2 2.5 mg

4

195

Mean Difference (IV, Fixed, 95% CI)

‐2.39 [‐5.18, 0.39]

2.3 5 mg

4

197

Mean Difference (IV, Fixed, 95% CI)

‐3.70 [‐6.38, ‐1.02]

2.4 10 mg

4

258

Mean Difference (IV, Fixed, 95% CI)

‐4.42 [‐6.54, ‐2.30]
Open in table viewer
Comparison 12. Spirapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 12.1
Comparison 12 Spirapril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 12 Spirapril vs Placebo, Outcome 1 Change in trough SBP.

1.1 3 mg

2

130

Mean Difference (IV, Fixed, 95% CI)

‐4.09 [‐10.47, 2.29]

1.2 6 mg

3

210

Mean Difference (IV, Fixed, 95% CI)

‐7.66 [‐11.93, ‐3.40]

1.3 12 mg (Max Dose)

2

146

Mean Difference (IV, Fixed, 95% CI)

‐8.46 [‐13.27, ‐3.66]

1.4 24 mg

2

139

Mean Difference (IV, Fixed, 95% CI)

‐9.67 [‐14.39, ‐4.95]

2 Change in trough DBP Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 12.2
Comparison 12 Spirapril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 12 Spirapril vs Placebo, Outcome 2 Change in trough DBP.

2.1 3 mg

2

130

Mean Difference (IV, Fixed, 95% CI)

‐3.91 [‐7.52, ‐0.29]

2.2 6 mg

4

359

Mean Difference (IV, Fixed, 95% CI)

‐6.52 [‐8.42, ‐4.62]

2.3 12 mg (Max Dose)

2

146

Mean Difference (IV, Fixed, 95% CI)

‐6.20 [‐9.20, ‐3.20]

2.4 24 mg

2

140

Mean Difference (IV, Fixed, 95% CI)

‐4.84 [‐7.86, ‐1.83]
Open in table viewer
Comparison 13. Temocapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 13.1
Comparison 13 Temocapril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 13 Temocapril vs Placebo, Outcome 1 Change in trough SBP.

1.1 20 mg

1

30

Mean Difference (IV, Fixed, 95% CI)

‐10.0 [‐23.87, 3.87]

2 Change in trough DBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 13.2
Comparison 13 Temocapril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 13 Temocapril vs Placebo, Outcome 2 Change in trough DBP.

2.1 20 mg

1

30

Mean Difference (IV, Fixed, 95% CI)

‐5.0 [‐13.34, 3.34]
Open in table viewer
Comparison 14. Trandolapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

10

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 14.1
Comparison 14 Trandolapril vs Placebo, Outcome 1 Change in trough SBP.

Comparison 14 Trandolapril vs Placebo, Outcome 1 Change in trough SBP.

1.1 0.25 mg

1

35

Mean Difference (IV, Fixed, 95% CI)

‐2.7 [‐13.26, 7.86]

1.2 0.5 mg

4

185

Mean Difference (IV, Fixed, 95% CI)

‐3.33 [‐6.00, 1.33]

1.3 1 mg

4

294

Mean Difference (IV, Fixed, 95% CI)

‐8.45 [‐11.84, ‐5.06]

1.4 2 mg

7

636

Mean Difference (IV, Fixed, 95% CI)

‐6.21 [‐8.76, ‐3.66]

1.5 4 mg (Max Dose)

3

430

Mean Difference (IV, Fixed, 95% CI)

‐8.15 [‐10.82, ‐5.49]

1.6 8 mg

2

111

Mean Difference (IV, Fixed, 95% CI)

‐5.74 [‐12.52, 1.05]

1.7 12 mg

1

49

Mean Difference (IV, Fixed, 95% CI)

‐5.7 [‐16.60, 5.20]

1.8 16 mg

1

48

Mean Difference (IV, Fixed, 95% CI)

‐7.10 [‐17.36, 3.16]

2 Change in trough DBP Show forest plot

10

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 14.2
Comparison 14 Trandolapril vs Placebo, Outcome 2 Change in trough DBP.

Comparison 14 Trandolapril vs Placebo, Outcome 2 Change in trough DBP.

2.1 0.25 mg

1

35

Mean Difference (IV, Fixed, 95% CI)

0.6 [‐4.46, 5.66]

2.2 0.5 mg

4

184

Mean Difference (IV, Fixed, 95% CI)

‐2.33 [‐4.90, 0.24]

2.3 1 mg

4

294

Mean Difference (IV, Fixed, 95% CI)

‐4.07 [‐5.89, ‐2.25]

2.4 2 mg

7

637

Mean Difference (IV, Fixed, 95% CI)

‐4.24 [‐5.55, ‐2.94]

2.5 4 mg (Max Dose)

3

431

Mean Difference (IV, Fixed, 95% CI)

‐4.62 [‐6.10, ‐3.13]

2.6 8 mg

2

110

Mean Difference (IV, Fixed, 95% CI)

‐4.41 [‐7.82, ‐1.01]

2.7 12 mg

1

49

Mean Difference (IV, Fixed, 95% CI)

‐6.2 [‐11.78, ‐0.62]

2.8 16 mg

1

48

Mean Difference (IV, Fixed, 95% CI)

‐6.2 [‐11.38, ‐1.02]
Open in table viewer
Comparison 15. 1/16 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

4

262

Mean Difference (IV, Fixed, 95% CI)

‐0.16 [‐3.78, 3.46]
Analysis 15.1
Comparison 15 1/16 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

Comparison 15 1/16 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

1.1 Fosinopril 2.5 mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐2.9 [‐9.93, 4.13]

1.2 Lisinopril 5 mg

1

76

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐9.79, 5.79]

1.3 Ramipril 1.25 mg

2

128

Mean Difference (IV, Fixed, 95% CI)

2.01 [‐3.02, 7.05]

2 Change in trough DBP Show forest plot

4

262

Mean Difference (IV, Fixed, 95% CI)

0.15 [‐1.86, 2.16]
Analysis 15.2
Comparison 15 1/16 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

Comparison 15 1/16 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

2.1 Fosinopril 2.5 mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐4.77, 3.37]

2.2 Lisinopril 5 mg

1

76

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐3.68, 3.68]

2.3 Ramipril 1.25 mg

2

128

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐2.28, 3.67]
Open in table viewer
Comparison 16. 1/8 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

18

2025

Mean Difference (IV, Fixed, 95% CI)

‐5.70 [‐6.95, ‐4.45]
Analysis 16.1
Comparison 16 1/8 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

Comparison 16 1/8 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

1.1 Benazepril 5 mg

2

91

Mean Difference (IV, Fixed, 95% CI)

‐6.39 [‐12.32, ‐0.47]

1.2 Enalapril 5 mg

4

607

Mean Difference (IV, Fixed, 95% CI)

‐5.12 [‐7.33, ‐2.92]

1.3 Fosinopril 5 mg

1

151

Mean Difference (IV, Fixed, 95% CI)

‐3.7 [‐8.06, 0.66]

1.4 Lisinopril 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐7.75 [‐9.98, ‐5.51]

1.5 Ramipril 2.5 mg

4

292

Mean Difference (IV, Fixed, 95% CI)

‐4.52 [‐8.05, ‐0.98]

1.6 Trandolapril 0.5 mg

3

236

Mean Difference (IV, Fixed, 95% CI)

‐4.19 [‐7.91, ‐0.46]

2 Change in trough DBP Show forest plot

19

2176

Mean Difference (IV, Fixed, 95% CI)

‐3.19 [‐3.88, ‐2.51]
Analysis 16.2
Comparison 16 1/8 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

Comparison 16 1/8 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

2.1 Benazepril 5 mg

2

91

Mean Difference (IV, Fixed, 95% CI)

‐1.92 [‐5.89, 2.05]

2.2 Enalapril 5 mg

5

758

Mean Difference (IV, Fixed, 95% CI)

‐2.37 [‐3.52, ‐1.23]

2.3 Fosinopril 5 mg

1

151

Mean Difference (IV, Fixed, 95% CI)

‐3.20 [‐5.72, ‐0.68]

2.4 Lisinopril 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐4.71 [‐5.92, ‐3.50]

2.5 Ramipril 2.5 mg

4

292

Mean Difference (IV, Fixed, 95% CI)

‐2.50 [‐4.50, ‐0.51]

2.6 Trandolapril 0.5 mg

3

236

Mean Difference (IV, Fixed, 95% CI)

‐2.46 [‐4.59, ‐0.33]
Open in table viewer
Comparison 17. 1/4 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

40

3523

Mean Difference (IV, Fixed, 95% CI)

‐5.14 [‐6.05, ‐4.22]
Analysis 17.1
Comparison 17 1/4 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

Comparison 17 1/4 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

1.1 Benazepril 10 mg

3

314

Mean Difference (IV, Fixed, 95% CI)

‐2.88 [‐5.92, 0.15]

1.2 Cilazapril 2.5 mg

9

462

Mean Difference (IV, Fixed, 95% CI)

‐4.76 [‐7.34, ‐2.18]

1.3 Enalapril 10 mg

8

1138

Mean Difference (IV, Fixed, 95% CI)

‐5.40 [‐6.93, ‐3.87]

1.4 Fosinopril 10 mg

3

239

Mean Difference (IV, Fixed, 95% CI)

‐3.93 [‐7.39, ‐0.46]

1.5 Imidapril 5 mg

1

68

Mean Difference (IV, Fixed, 95% CI)

‐4.90 [‐11.31, 1.51]

1.6 Lisinopril 20 mg

1

80

Mean Difference (IV, Fixed, 95% CI)

‐7.8 [‐14.38, ‐1.22]

1.7 Moexipril 7.5 mg

3

223

Mean Difference (IV, Fixed, 95% CI)

‐1.86 [‐5.86, 2.14]

1.8 Perindopril 2 mg

2

134

Mean Difference (IV, Fixed, 95% CI)

‐3.02 [‐9.36, 3.31]

1.9 Ramipril 5 mg

4

291

Mean Difference (IV, Fixed, 95% CI)

‐7.19 [‐10.71, ‐3.67]

1.10 Spirapril 3 mg

2

184

Mean Difference (IV, Fixed, 95% CI)

‐4.02 [‐8.33, 0.28]

1.11 Trandolapril 1 mg

4

390

Mean Difference (IV, Fixed, 95% CI)

‐7.74 [‐10.34, ‐5.15]

2 Change in trough DBP Show forest plot

43

3758

Mean Difference (IV, Fixed, 95% CI)

‐3.04 [‐3.53, ‐2.54]
Analysis 17.2
Comparison 17 1/4 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

Comparison 17 1/4 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

2.1 Benazepril 10 mg

3

314

Mean Difference (IV, Fixed, 95% CI)

‐0.89 [‐2.70, 0.93]

2.2 Cilazapril 2.5 mg

12

697

Mean Difference (IV, Fixed, 95% CI)

‐3.15 [‐4.29, 0.00]

2.3 Enalapril 10 mg

8

1138

Mean Difference (IV, Fixed, 95% CI)

‐3.11 [‐2.00, ‐2.23]

2.4 Fosinopril 10 mg

3

239

Mean Difference (IV, Fixed, 95% CI)

‐3.42 [‐5.43, ‐1.42]

2.5 Imidapril 5 mg

1

68

Mean Difference (IV, Fixed, 95% CI)

‐3.2 [‐7.41, 1.01]

2.6 Lisinopril 20 mg

1

80

Mean Difference (IV, Fixed, 95% CI)

‐4.6 [‐8.63, ‐0.57]

2.7 Moexipril 7.5 mg

3

223

Mean Difference (IV, Fixed, 95% CI)

‐2.18 [‐4.11, ‐0.24]

2.8 Perindopril 2 mg

2

134

Mean Difference (IV, Fixed, 95% CI)

‐2.31 [‐5.06, 0.45]

2.9 Ramipril 5 mg

4

291

Mean Difference (IV, Fixed, 95% CI)

‐3.65 [‐5.62, ‐1.67]

2.10 Spirapril 3 mg

2

184

Mean Difference (IV, Fixed, 95% CI)

‐4.20 [‐6.66, ‐1.74]

2.11 Trandolapril 1 mg

4

390

Mean Difference (IV, Fixed, 95% CI)

‐3.52 [‐4.92, ‐2.11]
Open in table viewer
Comparison 18. 1/2 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

51

4980

Mean Difference (IV, Fixed, 95% CI)

‐7.60 [‐8.40, ‐6.79]
Analysis 18.1
Comparison 18 1/2 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

Comparison 18 1/2 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

1.1 Benazepril 20 mg

6

504

Mean Difference (IV, Fixed, 95% CI)

‐7.97 [‐10.41, ‐5.52]

1.2 Cilazapril 5 mg

5

379

Mean Difference (IV, Fixed, 95% CI)

‐5.92 [‐8.70, ‐3.14]

1.3 Enalapril 20 mg

8

967

Mean Difference (IV, Fixed, 95% CI)

‐9.54 [‐11.22, ‐7.86]

1.4 Fosinopril 20 mg

5

277

Mean Difference (IV, Fixed, 95% CI)

‐8.99 [‐12.35, ‐5.62]

1.5 Imidapril 10 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐8.90 [‐16.26, ‐1.54]

1.6 Lisinopril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.7 Moexipril 15 mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐8.02 [‐11.16, ‐4.88]

1.8 Perindopril 4 mg

6

868

Mean Difference (IV, Fixed, 95% CI)

‐6.53 [‐9.04, ‐4.02]

1.9 Quinapril 20 mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐7.05 [‐11.26, ‐2.84]

1.10 Ramipril 10 mg

4

344

Mean Difference (IV, Fixed, 95% CI)

‐6.17 [‐9.07, ‐3.27]

1.11 Spirapril 6 mg

3

303

Mean Difference (IV, Fixed, 95% CI)

‐7.43 [‐10.41, ‐4.46]

1.12 Trandolapril 2 mg

7

769

Mean Difference (IV, Fixed, 95% CI)

‐6.17 [‐8.24, ‐4.10]

2 Change in trough DBP Show forest plot

57

5623

Mean Difference (IV, Fixed, 95% CI)

‐4.67 [‐5.09, ‐4.25]
Analysis 18.2
Comparison 18 1/2 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

Comparison 18 1/2 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

2.1 Benazepril 20 mg

6

504

Mean Difference (IV, Fixed, 95% CI)

‐4.30 [‐5.70, ‐2.90]

2.2 Cilazapril 5 mg

9

800

Mean Difference (IV, Fixed, 95% CI)

‐3.40 [‐4.45, ‐2.36]

2.3 Enalapril 20 mg

9

1039

Mean Difference (IV, Fixed, 95% CI)

‐5.29 [‐6.22, ‐4.37]

2.4 Fosinopril 20 mg

5

277

Mean Difference (IV, Fixed, 95% CI)

‐6.86 [‐8.70, ‐5.02]

2.5 Imidapril 10 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐7.40 [‐12.13, ‐2.67]

2.6 Lisinopril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.7 Moexipril 15 mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐4.26 [‐5.93, ‐2.60]

2.8 Perindopril 4 mg

6

868

Mean Difference (IV, Fixed, 95% CI)

‐4.81 [‐6.04, ‐3.58]

2.9 Quinapril 20 mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐3.35 [‐5.98, ‐0.72]

2.10 Ramipril 10 mg

4

344

Mean Difference (IV, Fixed, 95% CI)

‐4.47 [‐6.17, ‐2.76]

2.11 Spirapril 6 mg

4

453

Mean Difference (IV, Fixed, 95% CI)

‐5.92 [‐7.45, ‐4.39]

2.12 Trandolapril 2 mg

7

769

Mean Difference (IV, Fixed, 95% CI)

‐4.24 [‐5.35, ‐3.14]
Open in table viewer
Comparison 19. Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

16

1450

Mean Difference (IV, Fixed, 95% CI)

‐8.48 [‐9.91, ‐7.06]
Analysis 19.1
Comparison 19 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

Comparison 19 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

1.1 Benazepril 40 mg

2

112

Mean Difference (IV, Fixed, 95% CI)

‐8.67 [‐13.73, ‐3.62]

1.2 Cilazapril 10 mg

1

101

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐11.99, ‐2.01]

1.3 Enalapril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.4 Fosinopril 40 mg

3

245

Mean Difference (IV, Fixed, 95% CI)

‐7.78 [‐11.20, ‐4.36]

1.5 Imidapril 20 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐12.90 [‐20.56, ‐5.24]

1.6 Lisinopril 80 mg

1

79

Mean Difference (IV, Fixed, 95% CI)

‐13.8 [‐20.77, ‐6.83]

1.7 Moexipril 30 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.8 Perindopril 8 mg

2

129

Mean Difference (IV, Fixed, 95% CI)

‐10.09 [‐16.14, ‐4.05]

1.9 Quinapril 40 mg

1

14

Mean Difference (IV, Fixed, 95% CI)

‐6.0 [‐20.16, 8.16]

1.10 Ramipril 20 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.11 Spirapril 12 mg

2

226

Mean Difference (IV, Fixed, 95% CI)

‐8.23 [‐11.65, ‐4.82]

1.12 Trandolapril 4 mg

3

478

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐10.41, ‐5.59]

2 Change in trough DBP Show forest plot

17

1636

Mean Difference (IV, Fixed, 95% CI)

‐4.95 [‐5.71, ‐4.20]
Analysis 19.2
Comparison 19 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

Comparison 19 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

2.1 Benazepril 40 mg

2

112

Mean Difference (IV, Fixed, 95% CI)

‐4.76 [‐7.84, ‐1.69]

2.2 Cilazapril 10 mg

2

287

Mean Difference (IV, Fixed, 95% CI)

‐4.06 [‐5.74, ‐2.37]

2.3 Enalapril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Fosinopril 40 mg

3

245

Mean Difference (IV, Fixed, 95% CI)

‐4.63 [‐6.61, ‐2.65]

2.5 Imidapril 20 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐6.3 [‐10.88, ‐1.72]

2.6 Lisinopril 80 mg

1

79

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐9.96, ‐2.04]

2.7 Moexipril 30 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.8 Perindopril 8 mg

2

129

Mean Difference (IV, Fixed, 95% CI)

‐5.94 [‐8.81, ‐3.07]

2.9 Quinapril 40 mg

1

14

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐17.78, ‐0.22]

2.10 Ramipril 20 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.11 Spirapril 12 mg

2

226

Mean Difference (IV, Fixed, 95% CI)

‐6.02 [‐8.09, ‐3.96]

2.12 Trandolapril 4 mg

3

478

Mean Difference (IV, Fixed, 95% CI)

‐4.71 [‐6.05, ‐3.37]
Open in table viewer
Comparison 20. 2 Max and Higher Doses vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

7

738

Mean Difference (IV, Fixed, 95% CI)

‐8.81 [‐10.92, ‐6.70]
Analysis 20.1
Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.

Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.

1.1 Benazepril 80 mg

1

77

Mean Difference (IV, Fixed, 95% CI)

‐11.40 [‐17.51, ‐5.29]

1.2 Imidapril 40 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐10.60 [‐17.40, ‐3.80]

1.3 Perindopril 16 mg

1

108

Mean Difference (IV, Fixed, 95% CI)

‐8.9 [‐15.36, ‐2.44]

1.4 Spirapril 24 mg

2

220

Mean Difference (IV, Fixed, 95% CI)

‐9.40 [‐12.67, ‐6.12]

1.5 Trandolapril 8, 12, 16 mg

2

266

Mean Difference (IV, Fixed, 95% CI)

‐6.03 [‐10.14, ‐1.93]

2 Change in trough DBP Show forest plot

7

738

Mean Difference (IV, Fixed, 95% CI)

‐5.25 [‐6.45, ‐4.05]
Analysis 20.2
Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.

Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.

2.1 Benazepril 80 mg

1

77

Mean Difference (IV, Fixed, 95% CI)

‐6.80 [‐10.34, ‐3.26]

2.2 Imidapril 40 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐6.5 [‐11.22, ‐1.78]

2.3 Perindopril 16 mg

1

108

Mean Difference (IV, Fixed, 95% CI)

‐5.5 [‐8.48, ‐2.52]

2.4 Spirapril 24 mg

2

220

Mean Difference (IV, Fixed, 95% CI)

‐4.56 [‐6.66, ‐2.47]

2.5 Trandolapril 8, 12, 16 mg

2

266

Mean Difference (IV, Fixed, 95% CI)

‐5.02 [‐7.12, ‐2.93]
Open in table viewer
Comparison 21. 1/2 Max and Higher Doses vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

53

6113

Mean Difference (IV, Fixed, 95% CI)

‐7.85 [‐8.60, ‐7.09]
Analysis 21.1
Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.

Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.

1.1 Benazepril 20, 40, 80 mg

6

598

Mean Difference (IV, Fixed, 95% CI)

‐8.54 [‐10.87, ‐6.21]

1.2 Cilazapril 5, 10 mg

5

429

Mean Difference (IV, Fixed, 95% CI)

‐5.79 [‐8.46, ‐3.12]

1.3 Enalapril 20, (40) mg

8

967

Mean Difference (IV, Fixed, 95% CI)

‐9.54 [‐11.22, ‐7.86]

1.4 Fosinopril 20, 40 mg

4

359

Mean Difference (IV, Fixed, 95% CI)

‐7.44 [‐10.44, ‐4.44]

1.5 Imidapril 10, 20, 40 mg

1

129

Mean Difference (IV, Fixed, 95% CI)

‐10.8 [‐16.60, ‐5.00]

1.6 Lisinopril (40), 80 mg

1

50

Mean Difference (IV, Fixed, 95% CI)

‐13.8 [‐24.46, ‐3.14]

1.7 Moexipril 15, (30) mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐8.02 [‐11.16, ‐4.88]

1.8 Perindopril 4, 8, 16 mg

6

985

Mean Difference (IV, Fixed, 95% CI)

‐7.12 [‐9.55, ‐4.70]

1.9 Quinapril 20, (40) mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐7.05 [‐11.26, ‐2.84]

1.10 Ramipril 10, (20) mg

4

257

Mean Difference (IV, Fixed, 95% CI)

‐5.74 [‐9.33, ‐2.16]

1.11 Spirapril 6, 12, 24 mg

3

521

Mean Difference (IV, Fixed, 95% CI)

‐8.31 [‐10.80, ‐5.82]

1.12 Trandolapril 2, 4, 8, 12, 16 mg

9

1315

Mean Difference (IV, Fixed, 95% CI)

‐7.02 [‐8.70, ‐5.34]

2 Change in trough DBP Show forest plot

59

6861

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐5.13, ‐4.34]
Analysis 21.2
Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.

Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.

2.1 Benazepril 20, 40, 80 mg

6

598

Mean Difference (IV, Fixed, 95% CI)

‐4.56 [‐5.91, ‐3.22]

2.2 Cilazapril 5, 10 mg

9

942

Mean Difference (IV, Fixed, 95% CI)

‐3.58 [‐4.57, ‐2.60]

2.3 Enalapril 20, (40) mg

9

1039

Mean Difference (IV, Fixed, 95% CI)

‐5.29 [‐6.22, ‐4.37]

2.4 Fosinopril 20, 40 mg

4

359

Mean Difference (IV, Fixed, 95% CI)

‐5.15 [‐6.85, ‐3.45]

2.5 Imidapril 10, 20, 40 mg

1

129

Mean Difference (IV, Fixed, 95% CI)

‐6.7 [‐10.54, ‐2.86]

2.6 Lisinopril (40), 80 mg

1

79

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐9.96, ‐2.04]

2.7 Moexipril 15, (30) mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐4.26 [‐5.93, ‐2.60]

2.8 Perindopril 4, 8, 16 mg

6

985

Mean Difference (IV, Fixed, 95% CI)

‐5.01 [‐6.18, ‐3.84]

2.9 Quinapril 20, (40) mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐3.35 [‐5.98, ‐0.72]

2.10 Ramipril 10, (20) mg

4

257

Mean Difference (IV, Fixed, 95% CI)

‐4.42 [‐6.55, ‐2.29]

2.11 Spirapril 6, 12, 24 mg

4

671

Mean Difference (IV, Fixed, 95% CI)

‐5.84 [‐7.19, ‐4.49]

2.12 Trandolapril 2, 4, 8, 12, 16 mg

9

1299

Mean Difference (IV, Fixed, 95% CI)

‐4.65 [‐5.55, ‐3.74]
Open in table viewer
Comparison 22. ACE Inhibitors vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in peak SBP [1/2 Max and Higher Doses Only] Show forest plot

11

1154

Mean Difference (IV, Fixed, 95% CI)

‐11.53 [‐13.27, ‐9.78]
Analysis 22.1
Comparison 22 ACE Inhibitors vs Placebo, Outcome 1 Change in peak SBP [1/2 Max and Higher Doses Only].

Comparison 22 ACE Inhibitors vs Placebo, Outcome 1 Change in peak SBP [1/2 Max and Higher Doses Only].

1.1 1/2 Max Dose

11

783

Mean Difference (IV, Fixed, 95% CI)

‐11.06 [‐13.11, ‐9.02]

1.2 Max Dose

3

143

Mean Difference (IV, Fixed, 95% CI)

‐11.48 [‐17.37, ‐5.60]

1.3 2 Max Dose

3

228

Mean Difference (IV, Fixed, 95% CI)

‐13.36 [‐17.40, ‐9.31]

2 Change in peak DBP [1/2 Max and Higher Doses Only] Show forest plot

15

1485

Mean Difference (IV, Fixed, 95% CI)

‐6.37 [‐7.15, ‐5.58]
Analysis 22.2
Comparison 22 ACE Inhibitors vs Placebo, Outcome 2 Change in peak DBP [1/2 Max and Higher Doses Only].

Comparison 22 ACE Inhibitors vs Placebo, Outcome 2 Change in peak DBP [1/2 Max and Higher Doses Only].

2.1 1/2 Max Dose

15

1103

Mean Difference (IV, Fixed, 95% CI)

‐6.02 [‐6.95, ‐5.08]

2.2 Max Dose

4

157

Mean Difference (IV, Fixed, 95% CI)

‐6.49 [‐8.81, ‐4.16]

2.3 2 Max Dose

3

225

Mean Difference (IV, Fixed, 95% CI)

‐7.69 [‐9.56, ‐5.82]

3 Change in peak SBP [All Doses] Show forest plot

11

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 22.3
Comparison 22 ACE Inhibitors vs Placebo, Outcome 3 Change in peak SBP [All Doses].

Comparison 22 ACE Inhibitors vs Placebo, Outcome 3 Change in peak SBP [All Doses].

3.1 1/8 Max Dose

1

11

Mean Difference (IV, Fixed, 95% CI)

‐11.3 [‐30.46, 7.86]

3.2 1/4 Max Dose

6

326

Mean Difference (IV, Fixed, 95% CI)

‐6.03 [‐9.93, ‐2.13]

3.3 1/2 Max Dose

11

724

Mean Difference (IV, Fixed, 95% CI)

‐10.97 [‐13.14, ‐8.80]

3.4 Max Dose

3

136

Mean Difference (IV, Fixed, 95% CI)

‐11.43 [‐17.69, ‐5.16]

3.5 2 Max Dose

3

211

Mean Difference (IV, Fixed, 95% CI)

‐13.58 [‐18.03, ‐9.13]

4 Change in peak DBP [All Doses] Show forest plot

15

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 22.4
Comparison 22 ACE Inhibitors vs Placebo, Outcome 4 Change in peak DBP [All Doses].

Comparison 22 ACE Inhibitors vs Placebo, Outcome 4 Change in peak DBP [All Doses].

4.1 1/8 Max Dose

3

154

Mean Difference (IV, Fixed, 95% CI)

‐9.51 [‐12.64, ‐6.38]

4.2 1/4 Max Dose

9

451

Mean Difference (IV, Fixed, 95% CI)

‐3.69 [‐5.24, ‐2.15]

4.3 1/2 Max Dose

15

981

Mean Difference (IV, Fixed, 95% CI)

‐5.98 [‐7.02, ‐4.94]

4.4 Max Dose

4

157

Mean Difference (IV, Fixed, 95% CI)

‐6.49 [‐8.81, ‐4.16]

4.5 2 Max Dose

3

212

Mean Difference (IV, Fixed, 95% CI)

‐7.78 [‐9.74, ‐5.83]

5 Change in trough heart rate Show forest plot

16

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 22.5
Comparison 22 ACE Inhibitors vs Placebo, Outcome 5 Change in trough heart rate.

Comparison 22 ACE Inhibitors vs Placebo, Outcome 5 Change in trough heart rate.

5.1 1/8 Max Dose

1

114

Mean Difference (IV, Fixed, 95% CI)

‐3.0 [‐6.62, 0.62]

5.2 1/4 Max Dose

10

587

Mean Difference (IV, Fixed, 95% CI)

‐0.47 [‐1.76, 0.81]

5.3 1/2 Max Dose

9

917

Mean Difference (IV, Fixed, 95% CI)

‐0.71 [‐1.99, 0.57]

5.4 Max Dose

2

89

Mean Difference (IV, Fixed, 95% CI)

1.31 [‐2.15, 4.76]

6 Total withdrawals due to adverse effects Show forest plot

56

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 22.6
Comparison 22 ACE Inhibitors vs Placebo, Outcome 6 Total withdrawals due to adverse effects.

Comparison 22 ACE Inhibitors vs Placebo, Outcome 6 Total withdrawals due to adverse effects.

6.1 1/16 Max Dose

4

282

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.39, 2.57]

6.2 1/8 Max Dose

9

842

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.42, 1.82]

6.3 1/4 Max Dose

32

3385

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.42, 1.00]

6.4 1/2 Max Dose

38

3568

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.55, 1.19]

6.5 Max Dose

8

840

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.56, 2.35]

6.6 2 Max Dose

5

567

Risk Ratio (M‐H, Fixed, 95% CI)

1.51 [0.68, 3.34]

QUOROM flow diagram
Figuras y tablas -
Figure 1

QUOROM flow diagram

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Number of included studies according to publication year
Figuras y tablas -
Figure 2

Number of included studies according to publication year

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Number of included studies according to ACE inhibitor studied
Figuras y tablas -
Figure 3

Number of included studies according to ACE inhibitor studied

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Log dose‐response curve of benazepril 2 ‐ 80 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 4

Log dose‐response curve of benazepril 2 ‐ 80 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of captopril 37.5 ‐ 200 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 5

Log dose‐response curve of captopril 37.5 ‐ 200 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of cilazapril 0.5 ‐ 10 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 6

Log dose‐response curve of cilazapril 0.5 ‐ 10 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of enalapril 5 ‐ 40 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 7

Log dose‐response curve of enalapril 5 ‐ 40 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Lose dose‐response curve of fosinopril 2.5 ‐ 40 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 8

Lose dose‐response curve of fosinopril 2.5 ‐ 40 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of imidapril 5 ‐ 40 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 9

Log dose‐response curve of imidapril 5 ‐ 40 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Lose dose‐response curve of lisinopril 1.25 ‐ 80 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 10

Lose dose‐response curve of lisinopril 1.25 ‐ 80 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of moexipril 7.5 ‐ 30 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 11

Log dose‐response curve of moexipril 7.5 ‐ 30 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of perindopril 2 ‐ 16 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 12

Log dose‐response curve of perindopril 2 ‐ 16 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of quinapril 10 ‐ 40 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 13

Log dose‐response curve of quinapril 10 ‐ 40 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of ramipril 1.25 ‐ 20 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 14

Log dose‐response curve of ramipril 1.25 ‐ 20 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of spirapril 3 ‐ 24 mg/day
Figuras y tablas -
Figure 15

Log dose‐response curve of spirapril 3 ‐ 24 mg/day

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Log dose‐response curve of temocapril 1 ‐ 20 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 16

Log dose‐response curve of temocapril 1 ‐ 20 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Log dose‐response curve of trandolapril 0.5 ‐ 16 mg/day 
 (Shaded area represents manufacturer's recommended dose range)
Figuras y tablas -
Figure 17

Log dose‐response curve of trandolapril 0.5 ‐ 16 mg/day
(Shaded area represents manufacturer's recommended dose range)

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Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 18

Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 19

Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 20

Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 21

Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 22

Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 23

Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 24

Blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Log dose‐response curve of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 25

Log dose‐response curve of ACE inhibitors according to proportions of Max

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Near maximal blood pressure lowering efficacy of ACE inhibitors
Figuras y tablas -
Figure 26

Near maximal blood pressure lowering efficacy of ACE inhibitors

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Funnel plot of near maximal change in trough SBP for ACE inhibitors at 1/2 Max and higher doses
Figuras y tablas -
Figure 27

Funnel plot of near maximal change in trough SBP for ACE inhibitors at 1/2 Max and higher doses

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Funnel plot of near maximal change in trough DBP for ACE inhibitors at 1/2 Max and higher doses
Figuras y tablas -
Figure 28

Funnel plot of near maximal change in trough DBP for ACE inhibitors at 1/2 Max and higher doses

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Post‐hoc tertile analysis of the effect of trial size on reported trough BP lowering
Figuras y tablas -
Figure 29

Post‐hoc tertile analysis of the effect of trial size on reported trough BP lowering

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Post‐hoc tertile analysis of the effect of publication year on reported trough BP lowering
Figuras y tablas -
Figure 30

Post‐hoc tertile analysis of the effect of publication year on reported trough BP lowering

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Log dose‐response curve of peak blood pressure lowering efficacy of ACE inhibitors according to proportions of Max
Figuras y tablas -
Figure 31

Log dose‐response curve of peak blood pressure lowering efficacy of ACE inhibitors according to proportions of Max

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Log dose‐response curve assessing the effect of ACE inhibitors on heart rate
Figuras y tablas -
Figure 32

Log dose‐response curve assessing the effect of ACE inhibitors on heart rate

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Log dose‐response curve assessing the effect of ACE inhibitors on withdrawals due to adverse effects
Figuras y tablas -
Figure 33

Log dose‐response curve assessing the effect of ACE inhibitors on withdrawals due to adverse effects

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Comparison 1 Benazepril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 1.1

Comparison 1 Benazepril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 1 Benazepril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 1.2

Comparison 1 Benazepril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 2 Captopril vs Placebo, Outcome 1 Change in SBP.
Figuras y tablas -
Analysis 2.1

Comparison 2 Captopril vs Placebo, Outcome 1 Change in SBP.

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Comparison 2 Captopril vs Placebo, Outcome 2 Change in DBP.
Figuras y tablas -
Analysis 2.2

Comparison 2 Captopril vs Placebo, Outcome 2 Change in DBP.

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Comparison 3 Cilazapril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 3.1

Comparison 3 Cilazapril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 3 Cilazapril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 3.2

Comparison 3 Cilazapril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 4 Enalapril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 4.1

Comparison 4 Enalapril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 4 Enalapril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 4.2

Comparison 4 Enalapril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 5 Fosinopril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 5.1

Comparison 5 Fosinopril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 5 Fosinopril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 5.2

Comparison 5 Fosinopril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 6 Imidapril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 6.1

Comparison 6 Imidapril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 6 Imidapril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 6.2

Comparison 6 Imidapril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 7 Lisinopril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 7.1

Comparison 7 Lisinopril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 7 Lisinopril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 7.2

Comparison 7 Lisinopril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 8 Moexipril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 8.1

Comparison 8 Moexipril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 8 Moexipril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 8.2

Comparison 8 Moexipril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 9 Perindopril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 9.1

Comparison 9 Perindopril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 9 Perindopril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 9.2

Comparison 9 Perindopril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 10 Quinapril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 10.1

Comparison 10 Quinapril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 10 Quinapril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 10.2

Comparison 10 Quinapril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 11 Ramipril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 11.1

Comparison 11 Ramipril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 11 Ramipril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 11.2

Comparison 11 Ramipril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 12 Spirapril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 12.1

Comparison 12 Spirapril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 12 Spirapril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 12.2

Comparison 12 Spirapril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 13 Temocapril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 13.1

Comparison 13 Temocapril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 13 Temocapril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 13.2

Comparison 13 Temocapril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 14 Trandolapril vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 14.1

Comparison 14 Trandolapril vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 14 Trandolapril vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 14.2

Comparison 14 Trandolapril vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 15 1/16 Max Dose vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 15.1

Comparison 15 1/16 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 15 1/16 Max Dose vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 15.2

Comparison 15 1/16 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 16 1/8 Max Dose vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 16.1

Comparison 16 1/8 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 16 1/8 Max Dose vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 16.2

Comparison 16 1/8 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 17 1/4 Max Dose vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 17.1

Comparison 17 1/4 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 17 1/4 Max Dose vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 17.2

Comparison 17 1/4 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 18 1/2 Max Dose vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 18.1

Comparison 18 1/2 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 18 1/2 Max Dose vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 18.2

Comparison 18 1/2 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 19 Max Dose vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 19.1

Comparison 19 Max Dose vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 19 Max Dose vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 19.2

Comparison 19 Max Dose vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 20.1

Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 20.2

Comparison 20 2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.
Figuras y tablas -
Analysis 21.1

Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 1 Change in trough SBP.

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Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.
Figuras y tablas -
Analysis 21.2

Comparison 21 1/2 Max and Higher Doses vs Placebo, Outcome 2 Change in trough DBP.

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Comparison 22 ACE Inhibitors vs Placebo, Outcome 1 Change in peak SBP [1/2 Max and Higher Doses Only].
Figuras y tablas -
Analysis 22.1

Comparison 22 ACE Inhibitors vs Placebo, Outcome 1 Change in peak SBP [1/2 Max and Higher Doses Only].

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Comparison 22 ACE Inhibitors vs Placebo, Outcome 2 Change in peak DBP [1/2 Max and Higher Doses Only].
Figuras y tablas -
Analysis 22.2

Comparison 22 ACE Inhibitors vs Placebo, Outcome 2 Change in peak DBP [1/2 Max and Higher Doses Only].

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Comparison 22 ACE Inhibitors vs Placebo, Outcome 3 Change in peak SBP [All Doses].
Figuras y tablas -
Analysis 22.3

Comparison 22 ACE Inhibitors vs Placebo, Outcome 3 Change in peak SBP [All Doses].

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Comparison 22 ACE Inhibitors vs Placebo, Outcome 4 Change in peak DBP [All Doses].
Figuras y tablas -
Analysis 22.4

Comparison 22 ACE Inhibitors vs Placebo, Outcome 4 Change in peak DBP [All Doses].

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Comparison 22 ACE Inhibitors vs Placebo, Outcome 5 Change in trough heart rate.
Figuras y tablas -
Analysis 22.5

Comparison 22 ACE Inhibitors vs Placebo, Outcome 5 Change in trough heart rate.

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Comparison 22 ACE Inhibitors vs Placebo, Outcome 6 Total withdrawals due to adverse effects.
Figuras y tablas -
Analysis 22.6

Comparison 22 ACE Inhibitors vs Placebo, Outcome 6 Total withdrawals due to adverse effects.

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Table 1. Overview of the 92 included studies investigating ACE inhibitors as monotherapy

ACE inhibitor

Dose range (mg/day)

Number of studies

ACEI patients (n)

Placebo patients (n)

Mean duration (wks)

Mean age (yrs)

Baseline BP (mm Hg)

Baseline PP (mm Hg)

Benazepril

2 ‐ 80

7

591

335

6.0

56.3

159.5/103.5

56.0

Captopril

37.5 ‐ 200

6

660

383

6.5

54.9

155.0/100.1

54.9

Cilazapril

0.5 ‐ 10

14

1054

448

4.9

53.3

153.5/101.0

52.5

Enalapril

5 ‐ 20

19

1477

1331

6.5

54.2

157.5/100.5

57.0

Fosinopril

2.5 ‐ 40

6

481

168

5.0

52.5

152.1/101.2

50.9

Imidapril

5 ‐ 40

1

127

35

4.0

51.9

160.7/101.5

59.2

Lisinopril

1.25 ‐ 80

5

484

357

5.7

55.2

154.5/101.8

52.7

Moexipril

7.5 ‐ 15

4

274

159

10.7

60.5

160.4/101.7

58.7

Perindopril

2 ‐ 16

6

658

396

7.1

55.9

159.4/99.9

59.5

Quinapril

20

3

99

97

4.0

52.6

161.7/105.6

56.1

Ramipril

1.25 ‐ 10

6

548

199

6.6

51.2

156.6/100.9

55.7

Spirapril

3 ‐24

4

586

189

5.6

52.3

164.3/103.5

60.8

Temocapril

20

1

19

11

6.0

57.0

158.0/97.6

60.4

Trandolapril

0.25 ‐ 16

10

1152

636

6.1

53.4

155.4/100.7

54.7

TOTAL

92

8210

4744

6.2

54.4

157.1/101.2

55.9
Figuras y tablas -
Table 1. Overview of the 92 included studies investigating ACE inhibitors as monotherapy
Ir a la tabla de la revisión
Table 2. Summary of the blood pressure lowering efficacy of ACE inhibitors

ACE Inhibitor

Lowest effective dose (mg/day)

Lowest dose with near maximal BP lowering (mg/day)

Near maximal trough SBP lowering (mm Hg), 95% CI

Near maximal trough DBP lowering (mm Hg), 95% CI

benazepril

20

20

‐8.70 (‐11.43, ‐5.97)

‐4.92 (‐6.47, ‐3.36)

captopril

37.5

37.5

‐9.68 (‐11.73, ‐7.63)

‐5.43 (‐6.47, ‐4.40)

cilazapril

2.5

2.5

‐5.58 (‐7.84, ‐3.32)

‐3.50 (‐4.40, ‐2.60)

enalapril

5

20

‐8.66 (‐10.48, ‐6.84)

‐4.80 (‐5.81, ‐3.79)

fosinopril

10‐20

20

‐7.62 (‐11.07, ‐4.17)

‐5.00 (‐6.94, ‐3.05)

imidapril

Not estimable

Not estimable

‐9.30 (‐14.83, ‐3.78)

‐5.76 (‐9.44, ‐2.07)

lisinopril

10

10

‐8.00 (‐10.14, ‐5.85)

‐4.76 (‐5.92, ‐3.60)

moexipril

15

Not estimable

‐8.45 (‐11.99, ‐4.91)

‐4.38 (‐6.29, ‐2.46)

perindopril

4

4

‐7.09 (‐9.56, ‐4.61)

‐5.02 (‐6.22, ‐3.82)

quinapril

Not estimable

Not estimable

‐7.05 (‐11.26, ‐2.84)

‐3.35 (‐5.98, ‐0.72)

ramipril

5

5

‐6.29 (‐9.26, ‐3.32)

‐4.14 (‐5.81, ‐2.48)

spirapril

3‐6

6

‐8.54 (‐11.18, ‐5.89)

‐6.08( ‐7.50, ‐4.66)

temocapril

Not estimable

Not estimable

‐10.00 (‐23.87, 3.87)

‐5.00 (‐13.34, 3.34)

trandolapril

1

1

‐7.31 (‐8.85, ‐5.77)

‐4.42 (‐5.24, ‐3.60)
Figuras y tablas -
Table 2. Summary of the blood pressure lowering efficacy of ACE inhibitors
Ir a la tabla de la revisión
Table 3. Variability of SBP and DBP at end of treatment

ACE Inhibitor

Placebo

SBP

Weighted mean SD

16.6

16.8

SD of weighted mean SD

3.1

3.0

Weighted mean SBP

146.0

152.9

Weighted mean coefficient of variation (CV)

11.2

11.0

SD of weighted mean CV

2.1

2.0

Number of observations

22

19

DBP

Weighted mean SD

9.0

8.9

SD of weighted mean SD

1.7

1.8

Weighted mean DBP

91.8

96.4

Weighted mean coefficient of variation (CV)

9.8

9.2

SD of weighted mean CV

1.8

1.9

Number of observations

20

18

t‐test

SD of SBP vs SD of DBP

p < 0.0001

p < 0.0001

t‐test

CV SBP vs CV DBP

p = 0.0227

p = 0.0045
Figuras y tablas -
Table 3. Variability of SBP and DBP at end of treatment
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Table 4. SD of BP at baseline vs endpoint in trials with DBP entry criteria

ACE Inhibitor

Placebo

Weighted mean SD of SBP

At baseline (SD)

14.8 (3.0)

14.9 (2.8)

At endpoint (SD)

16.6 (3.1)

16.8 (3.0)

t‐test

baseline vs endpoint

p = 0.06

p = 0.05

Weighted mean SD of DBP

At baseline (SD)

5.1 (1.5)

5.1 (1.6)

At endpoint (SD)

9.0 (1.7)

8.9 (1.8)

t‐test

baseline vs endpoint

p < 0.0001

p < 0.0001
Figuras y tablas -
Table 4. SD of BP at baseline vs endpoint in trials with DBP entry criteria
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Table 5. Change in pulse pressure according to proportions of Max

Proportion of recommended maximum dose (Max)

Number of studies

Weighted mean change from baseline in pulse pressure (95% CI)

ACE inhibitors

1/8 Max

18

‐1.2 (‐2.0, ‐0.4)

1/4 Max

40

‐1.8 (‐2.6, ‐0.9)

1/2 Max

50

‐2.5 (‐3.2, ‐1.9)

Max

16

‐3.7 (‐5.5, ‐1.9)

2 Max

6

‐4.1 (‐6.3, ‐1.9)

1/2 Max and above

54

‐2.9 (‐3.5, ‐2.3)

Placebo

74

0.6 (0.1, 1.1)
Figuras y tablas -
Table 5. Change in pulse pressure according to proportions of Max
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Table 6. Comparison of manufacturers' dosage recommendations and findings of this review

ACE Inhibitor

Lowest effective dose (mg/day)

Manufacturer's recommended starting dose (mg/day)

Lowest dose with near maximal BP lowering (mg/day)

Manufacturer's recommended maximum dose (mg/day)

benazepril

20

10

20

40

captopril

37.5

50

37.5

150

cilazapril

2.5

2.5

2.5

10

enalapril

5

5

20

40

fosinopril

10‐20

10

20

40

imidapril

Not estimable

5

Not estimable

30

lisinopril

10

10

10

80

moexipril

15

7.5

Not estimable

30

perindopril

4

4

4

8

quinapril

Not estimable

10

Not estimable

40

ramipril

5

2.5

5

20

temocapril

Not estimable

1

Not estimable

4

trandolapril

1

1

1

4
Figuras y tablas -
Table 6. Comparison of manufacturers' dosage recommendations and findings of this review
Ir a la tabla de la revisión
Comparison 1. Benazepril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

7

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 2 mg

1

36

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐11.87, 12.27]

1.2 4 mg

1

71

Mean Difference (IV, Fixed, 95% CI)

‐5.5 [‐12.17, 1.17]

1.3 5 mg

2

60

Mean Difference (IV, Fixed, 95% CI)

‐6.52 [‐16.09, 3.06]

1.4 10 mg

3

284

Mean Difference (IV, Fixed, 95% CI)

‐2.68 [‐5.98, 0.61]

1.5 20 mg

6

422

Mean Difference (IV, Fixed, 95% CI)

‐8.30 [‐11.14, ‐5.46]

1.6 40 mg (Max Dose)

2

74

Mean Difference (IV, Fixed, 95% CI)

‐8.68 [‐14.00, ‐1.35]

1.7 80 mg

1

50

Mean Difference (IV, Fixed, 95% CI)

‐11.40 [‐19.95, ‐2.85]

2 Change in trough DBP Show forest plot

7

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 2 mg

1

36

Mean Difference (IV, Fixed, 95% CI)

1.1 [‐6.54, 8.74]

2.2 4 mg

1

71

Mean Difference (IV, Fixed, 95% CI)

‐4.10 [‐7.95, ‐0.25]

2.3 5 mg

2

60

Mean Difference (IV, Fixed, 95% CI)

‐2.04 [‐8.60, 4.53]

2.4 10 mg

3

283

Mean Difference (IV, Fixed, 95% CI)

‐0.72 [‐2.67, 1.22]

2.5 20 mg

6

422

Mean Difference (IV, Fixed, 95% CI)

‐4.53 [‐6.14, ‐2.93]

2.6 40 mg (Max Dose)

2

74

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐9.15, ‐0.31]

2.7 80 mg

1

51

Mean Difference (IV, Fixed, 95% CI)

‐6.80 [‐11.60, 0.00]
Figuras y tablas -
Comparison 1. Benazepril vs Placebo
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Comparison 2. Captopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in SBP Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 37.5 mg

1

111

Mean Difference (IV, Fixed, 95% CI)

‐8.6 [‐14.95, ‐2.25]

1.2 50 mg

3

324

Mean Difference (IV, Fixed, 95% CI)

‐8.25 [‐11.34, ‐5.16]

1.3 75 mg

2

124

Mean Difference (IV, Fixed, 95% CI)

‐9.16 [‐15.09, ‐3.23]

1.4 100 mg

1

96

Mean Difference (IV, Fixed, 95% CI)

‐12.0 [‐18.17, ‐5.83]

1.5 150 mg (Max Dose)

1

117

Mean Difference (IV, Fixed, 95% CI)

‐12.0 [‐18.06, ‐5.94]

1.6 200 mg

1

94

Mean Difference (IV, Fixed, 95% CI)

‐12.20 [‐18.32, ‐6.08]

2 Change in DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 37.5 mg

1

111

Mean Difference (IV, Fixed, 95% CI)

‐5.40 [‐8.74, ‐2.06]

2.2 50 mg

4

500

Mean Difference (IV, Fixed, 95% CI)

‐4.58 [‐6.02, ‐3.15]

2.3 75 mg

2

124

Mean Difference (IV, Fixed, 95% CI)

‐5.92 [‐9.16, ‐2.68]

2.4 100 mg

1

97

Mean Difference (IV, Fixed, 95% CI)

‐6.4 [‐9.91, ‐2.89]

2.5 150 mg (Max Dose)

1

117

Mean Difference (IV, Fixed, 95% CI)

‐7.3 [‐10.43, ‐4.17]

2.6 200 mg

1

94

Mean Difference (IV, Fixed, 95% CI)

‐6.70 [‐10.23, ‐3.17]
Figuras y tablas -
Comparison 2. Captopril vs Placebo
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Comparison 3. Cilazapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

9

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 2.5 mg

9

361

Mean Difference (IV, Fixed, 95% CI)

‐5.16 [‐8.32, 0.00]

1.2 5 mg

5

277

Mean Difference (IV, Fixed, 95% CI)

‐5.75 [‐9.38, ‐2.12]

1.3 10 mg (Max Dose)

1

67

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐14.07, 0.07]

2 Change in trough DBP Show forest plot

14

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 0.5 mg

1

129

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐3.45, 2.45]

2.2 1 mg

1

56

Mean Difference (IV, Fixed, 95% CI)

1.1 [‐3.66, 5.86]

2.3 2.5 mg

13

558

Mean Difference (IV, Fixed, 95% CI)

‐3.32 [‐4.70, ‐1.94]

2.4 5 mg

9

569

Mean Difference (IV, Fixed, 95% CI)

‐3.49 [‐4.87, ‐2.11]

2.5 10 mg (Max Dose)

2

190

Mean Difference (IV, Fixed, 95% CI)

‐4.06 [‐6.44, ‐1.67]
Figuras y tablas -
Comparison 3. Cilazapril vs Placebo
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Comparison 4. Enalapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

17

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 5 mg

4

552

Mean Difference (IV, Fixed, 95% CI)

‐5.56 [‐7.95, ‐3.18]

1.2 10 mg

8

1122

Mean Difference (IV, Fixed, 95% CI)

‐5.42 [‐5.00, ‐3.84]

1.3 20 mg

8

911

Mean Difference (IV, Fixed, 95% CI)

‐9.61 [‐11.35, ‐7.86]

2 Change in trough DBP Show forest plot

19

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 5 mg

5

702

Mean Difference (IV, Fixed, 95% CI)

‐2.46 [‐3.67, ‐1.25]

2.2 10 mg

8

1122

Mean Difference (IV, Fixed, 95% CI)

‐3.10 [‐3.99, ‐2.20]

2.3 20 mg

9

984

Mean Difference (IV, Fixed, 95% CI)

‐5.34 [‐6.29, ‐4.38]
Figuras y tablas -
Comparison 4. Enalapril vs Placebo
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Comparison 5. Fosinopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 2.5 mg

1

38

Mean Difference (IV, Fixed, 95% CI)

‐2.9 [‐13.01, 7.21]

1.2 5 mg

1

94

Mean Difference (IV, Fixed, 95% CI)

‐3.70 [‐10.37, 2.97]

1.3 10 mg

3

151

Mean Difference (IV, Fixed, 95% CI)

‐3.86 [‐9.03, 1.30]

1.4 20 mg

5

208

Mean Difference (IV, Fixed, 95% CI)

‐9.26 [‐13.72, ‐4.79]

1.5 40 mg (Max Dose)

3

158

Mean Difference (IV, Fixed, 95% CI)

‐7.81 [‐12.91, ‐2.72]

2 Change in trough DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 2.5 mg

1

39

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐6.31, 4.91]

2.2 5 mg

1

93

Mean Difference (IV, Fixed, 95% CI)

‐3.20 [‐7.12, 0.72]

2.3 10 mg

3

151

Mean Difference (IV, Fixed, 95% CI)

‐3.45 [‐6.42, ‐0.47]

2.4 20 mg

5

209

Mean Difference (IV, Fixed, 95% CI)

‐7.79 [‐10.12, ‐5.46]

2.5 40 mg (Max Dose)

3

157

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐7.69, ‐1.76]
Figuras y tablas -
Comparison 5. Fosinopril vs Placebo
Ir a la tabla de la revisión
Comparison 6. Imidapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 5 mg

1

41

Mean Difference (IV, Fixed, 95% CI)

‐4.90 [‐15.96, 6.16]

1.2 10 mg

1

40

Mean Difference (IV, Fixed, 95% CI)

‐8.90 [‐20.02, 2.22]

1.3 20 mg (Max Dose)

1

40

Mean Difference (IV, Fixed, 95% CI)

‐12.90 [‐24.22, ‐1.58]

1.4 40 mg

1

41

Mean Difference (IV, Fixed, 95% CI)

‐10.60 [‐21.36, 0.16]

2 Change in trough DBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 5 mg

1

42

Mean Difference (IV, Fixed, 95% CI)

‐3.2 [‐10.28, 3.88]

2.2 10 mg

1

39

Mean Difference (IV, Fixed, 95% CI)

‐7.40 [‐15.16, 0.36]

2.3 20 mg (Max Dose)

1

40

Mean Difference (IV, Fixed, 95% CI)

‐6.3 [‐13.60, 1.00]

2.4 40 mg

1

41

Mean Difference (IV, Fixed, 95% CI)

‐6.50 [‐13.89, 0.89]
Figuras y tablas -
Comparison 6. Imidapril vs Placebo
Ir a la tabla de la revisión
Comparison 7. Lisinopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 1.25 mg

1

46

Mean Difference (IV, Fixed, 95% CI)

3.2 [‐5.00, 13.40]

1.2 5 mg

1

47

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐13.22, 9.22]

1.3 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐7.75 [‐9.98, ‐5.51]

1.4 20 mg

1

50

Mean Difference (IV, Fixed, 95% CI)

‐7.80 [‐18.67, 3.07]

1.5 80 mg (Max Dose)

1

50

Mean Difference (IV, Fixed, 95% CI)

‐13.8 [‐24.46, ‐3.14]

2 Change in trough DBP Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 1.25 mg

1

46

Mean Difference (IV, Fixed, 95% CI)

2.8 [‐2.34, 7.94]

2.2 5 mg

1

47

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐5.32, 5.32]

2.3 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐4.71 [‐5.92, ‐3.50]

2.4 20 mg

1

51

Mean Difference (IV, Fixed, 95% CI)

‐4.6 [‐10.17, 0.97]

2.5 80 mg (Max Dose)

1

49

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐11.72, ‐0.28]
Figuras y tablas -
Comparison 7. Lisinopril vs Placebo
Ir a la tabla de la revisión
Comparison 8. Moexipril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 7.5 mg

3

168

Mean Difference (IV, Fixed, 95% CI)

‐1.83 [‐6.71, 3.05]

1.2 15 mg

4

265

Mean Difference (IV, Fixed, 95% CI)

‐8.45 [‐11.99, ‐4.91]

2 Change in trough DBP Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 7.5 mg

3

167

Mean Difference (IV, Fixed, 95% CI)

‐2.23 [‐4.63, 0.16]

2.2 15 mg

4

266

Mean Difference (IV, Fixed, 95% CI)

‐4.38 [‐6.29, ‐2.46]
Figuras y tablas -
Comparison 8. Moexipril vs Placebo
Ir a la tabla de la revisión
Comparison 9. Perindopril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 2 mg

2

85

Mean Difference (IV, Fixed, 95% CI)

‐3.24 [‐13.20, 6.72]

1.2 4 mg

6

820

Mean Difference (IV, Fixed, 95% CI)

‐6.76 [‐9.41, ‐4.12]

1.3 8 mg (Max Dose)

2

82

Mean Difference (IV, Fixed, 95% CI)

‐9.81 [‐19.32, ‐0.31]

1.4 16 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐8.9 [‐19.65, 1.85]

2 Change in trough DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 2 mg

2

85

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐6.40, 2.20]

2.2 4 mg

6

820

Mean Difference (IV, Fixed, 95% CI)

‐4.91 [‐6.21, ‐3.61]

2.3 8 mg (Max Dose)

2

82

Mean Difference (IV, Fixed, 95% CI)

‐5.81 [‐10.11, ‐1.52]

2.4 16 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐5.50 [‐10.09, ‐0.91]
Figuras y tablas -
Comparison 9. Perindopril vs Placebo
Ir a la tabla de la revisión
Comparison 10. Quinapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 20 mg

3

196

Mean Difference (IV, Fixed, 95% CI)

‐5.87 [‐9.75, ‐1.99]

2 Change in trough DBP Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 20 mg

3

196

Mean Difference (IV, Fixed, 95% CI)

‐3.26 [‐5.85, ‐0.68]
Figuras y tablas -
Comparison 10. Quinapril vs Placebo
Ir a la tabla de la revisión
Comparison 11. Ramipril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 1.25 mg

2

98

Mean Difference (IV, Fixed, 95% CI)

4.06 [‐1.97, 10.08]

1.2 2.5 mg

4

197

Mean Difference (IV, Fixed, 95% CI)

‐4.38 [‐9.71, 0.95]

1.3 5 mg

4

195

Mean Difference (IV, Fixed, 95% CI)

‐7.47 [‐12.76, ‐2.19]

1.4 10 mg

4

257

Mean Difference (IV, Fixed, 95% CI)

‐5.74 [‐9.33, ‐2.16]

2 Change in trough DBP Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 1.25 mg

2

97

Mean Difference (IV, Fixed, 95% CI)

1.78 [‐1.83, 5.39]

2.2 2.5 mg

4

195

Mean Difference (IV, Fixed, 95% CI)

‐2.39 [‐5.18, 0.39]

2.3 5 mg

4

197

Mean Difference (IV, Fixed, 95% CI)

‐3.70 [‐6.38, ‐1.02]

2.4 10 mg

4

258

Mean Difference (IV, Fixed, 95% CI)

‐4.42 [‐6.54, ‐2.30]
Figuras y tablas -
Comparison 11. Ramipril vs Placebo
Ir a la tabla de la revisión
Comparison 12. Spirapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 3 mg

2

130

Mean Difference (IV, Fixed, 95% CI)

‐4.09 [‐10.47, 2.29]

1.2 6 mg

3

210

Mean Difference (IV, Fixed, 95% CI)

‐7.66 [‐11.93, ‐3.40]

1.3 12 mg (Max Dose)

2

146

Mean Difference (IV, Fixed, 95% CI)

‐8.46 [‐13.27, ‐3.66]

1.4 24 mg

2

139

Mean Difference (IV, Fixed, 95% CI)

‐9.67 [‐14.39, ‐4.95]

2 Change in trough DBP Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 3 mg

2

130

Mean Difference (IV, Fixed, 95% CI)

‐3.91 [‐7.52, ‐0.29]

2.2 6 mg

4

359

Mean Difference (IV, Fixed, 95% CI)

‐6.52 [‐8.42, ‐4.62]

2.3 12 mg (Max Dose)

2

146

Mean Difference (IV, Fixed, 95% CI)

‐6.20 [‐9.20, ‐3.20]

2.4 24 mg

2

140

Mean Difference (IV, Fixed, 95% CI)

‐4.84 [‐7.86, ‐1.83]
Figuras y tablas -
Comparison 12. Spirapril vs Placebo
Ir a la tabla de la revisión
Comparison 13. Temocapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 20 mg

1

30

Mean Difference (IV, Fixed, 95% CI)

‐10.0 [‐23.87, 3.87]

2 Change in trough DBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 20 mg

1

30

Mean Difference (IV, Fixed, 95% CI)

‐5.0 [‐13.34, 3.34]
Figuras y tablas -
Comparison 13. Temocapril vs Placebo
Ir a la tabla de la revisión
Comparison 14. Trandolapril vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

10

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 0.25 mg

1

35

Mean Difference (IV, Fixed, 95% CI)

‐2.7 [‐13.26, 7.86]

1.2 0.5 mg

4

185

Mean Difference (IV, Fixed, 95% CI)

‐3.33 [‐6.00, 1.33]

1.3 1 mg

4

294

Mean Difference (IV, Fixed, 95% CI)

‐8.45 [‐11.84, ‐5.06]

1.4 2 mg

7

636

Mean Difference (IV, Fixed, 95% CI)

‐6.21 [‐8.76, ‐3.66]

1.5 4 mg (Max Dose)

3

430

Mean Difference (IV, Fixed, 95% CI)

‐8.15 [‐10.82, ‐5.49]

1.6 8 mg

2

111

Mean Difference (IV, Fixed, 95% CI)

‐5.74 [‐12.52, 1.05]

1.7 12 mg

1

49

Mean Difference (IV, Fixed, 95% CI)

‐5.7 [‐16.60, 5.20]

1.8 16 mg

1

48

Mean Difference (IV, Fixed, 95% CI)

‐7.10 [‐17.36, 3.16]

2 Change in trough DBP Show forest plot

10

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 0.25 mg

1

35

Mean Difference (IV, Fixed, 95% CI)

0.6 [‐4.46, 5.66]

2.2 0.5 mg

4

184

Mean Difference (IV, Fixed, 95% CI)

‐2.33 [‐4.90, 0.24]

2.3 1 mg

4

294

Mean Difference (IV, Fixed, 95% CI)

‐4.07 [‐5.89, ‐2.25]

2.4 2 mg

7

637

Mean Difference (IV, Fixed, 95% CI)

‐4.24 [‐5.55, ‐2.94]

2.5 4 mg (Max Dose)

3

431

Mean Difference (IV, Fixed, 95% CI)

‐4.62 [‐6.10, ‐3.13]

2.6 8 mg

2

110

Mean Difference (IV, Fixed, 95% CI)

‐4.41 [‐7.82, ‐1.01]

2.7 12 mg

1

49

Mean Difference (IV, Fixed, 95% CI)

‐6.2 [‐11.78, ‐0.62]

2.8 16 mg

1

48

Mean Difference (IV, Fixed, 95% CI)

‐6.2 [‐11.38, ‐1.02]
Figuras y tablas -
Comparison 14. Trandolapril vs Placebo
Ir a la tabla de la revisión
Comparison 15. 1/16 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

4

262

Mean Difference (IV, Fixed, 95% CI)

‐0.16 [‐3.78, 3.46]

1.1 Fosinopril 2.5 mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐2.9 [‐9.93, 4.13]

1.2 Lisinopril 5 mg

1

76

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐9.79, 5.79]

1.3 Ramipril 1.25 mg

2

128

Mean Difference (IV, Fixed, 95% CI)

2.01 [‐3.02, 7.05]

2 Change in trough DBP Show forest plot

4

262

Mean Difference (IV, Fixed, 95% CI)

0.15 [‐1.86, 2.16]

2.1 Fosinopril 2.5 mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐4.77, 3.37]

2.2 Lisinopril 5 mg

1

76

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐3.68, 3.68]

2.3 Ramipril 1.25 mg

2

128

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐2.28, 3.67]
Figuras y tablas -
Comparison 15. 1/16 Max Dose vs Placebo
Ir a la tabla de la revisión
Comparison 16. 1/8 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

18

2025

Mean Difference (IV, Fixed, 95% CI)

‐5.70 [‐6.95, ‐4.45]

1.1 Benazepril 5 mg

2

91

Mean Difference (IV, Fixed, 95% CI)

‐6.39 [‐12.32, ‐0.47]

1.2 Enalapril 5 mg

4

607

Mean Difference (IV, Fixed, 95% CI)

‐5.12 [‐7.33, ‐2.92]

1.3 Fosinopril 5 mg

1

151

Mean Difference (IV, Fixed, 95% CI)

‐3.7 [‐8.06, 0.66]

1.4 Lisinopril 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐7.75 [‐9.98, ‐5.51]

1.5 Ramipril 2.5 mg

4

292

Mean Difference (IV, Fixed, 95% CI)

‐4.52 [‐8.05, ‐0.98]

1.6 Trandolapril 0.5 mg

3

236

Mean Difference (IV, Fixed, 95% CI)

‐4.19 [‐7.91, ‐0.46]

2 Change in trough DBP Show forest plot

19

2176

Mean Difference (IV, Fixed, 95% CI)

‐3.19 [‐3.88, ‐2.51]

2.1 Benazepril 5 mg

2

91

Mean Difference (IV, Fixed, 95% CI)

‐1.92 [‐5.89, 2.05]

2.2 Enalapril 5 mg

5

758

Mean Difference (IV, Fixed, 95% CI)

‐2.37 [‐3.52, ‐1.23]

2.3 Fosinopril 5 mg

1

151

Mean Difference (IV, Fixed, 95% CI)

‐3.20 [‐5.72, ‐0.68]

2.4 Lisinopril 10 mg

4

648

Mean Difference (IV, Fixed, 95% CI)

‐4.71 [‐5.92, ‐3.50]

2.5 Ramipril 2.5 mg

4

292

Mean Difference (IV, Fixed, 95% CI)

‐2.50 [‐4.50, ‐0.51]

2.6 Trandolapril 0.5 mg

3

236

Mean Difference (IV, Fixed, 95% CI)

‐2.46 [‐4.59, ‐0.33]
Figuras y tablas -
Comparison 16. 1/8 Max Dose vs Placebo
Ir a la tabla de la revisión
Comparison 17. 1/4 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

40

3523

Mean Difference (IV, Fixed, 95% CI)

‐5.14 [‐6.05, ‐4.22]

1.1 Benazepril 10 mg

3

314

Mean Difference (IV, Fixed, 95% CI)

‐2.88 [‐5.92, 0.15]

1.2 Cilazapril 2.5 mg

9

462

Mean Difference (IV, Fixed, 95% CI)

‐4.76 [‐7.34, ‐2.18]

1.3 Enalapril 10 mg

8

1138

Mean Difference (IV, Fixed, 95% CI)

‐5.40 [‐6.93, ‐3.87]

1.4 Fosinopril 10 mg

3

239

Mean Difference (IV, Fixed, 95% CI)

‐3.93 [‐7.39, ‐0.46]

1.5 Imidapril 5 mg

1

68

Mean Difference (IV, Fixed, 95% CI)

‐4.90 [‐11.31, 1.51]

1.6 Lisinopril 20 mg

1

80

Mean Difference (IV, Fixed, 95% CI)

‐7.8 [‐14.38, ‐1.22]

1.7 Moexipril 7.5 mg

3

223

Mean Difference (IV, Fixed, 95% CI)

‐1.86 [‐5.86, 2.14]

1.8 Perindopril 2 mg

2

134

Mean Difference (IV, Fixed, 95% CI)

‐3.02 [‐9.36, 3.31]

1.9 Ramipril 5 mg

4

291

Mean Difference (IV, Fixed, 95% CI)

‐7.19 [‐10.71, ‐3.67]

1.10 Spirapril 3 mg

2

184

Mean Difference (IV, Fixed, 95% CI)

‐4.02 [‐8.33, 0.28]

1.11 Trandolapril 1 mg

4

390

Mean Difference (IV, Fixed, 95% CI)

‐7.74 [‐10.34, ‐5.15]

2 Change in trough DBP Show forest plot

43

3758

Mean Difference (IV, Fixed, 95% CI)

‐3.04 [‐3.53, ‐2.54]

2.1 Benazepril 10 mg

3

314

Mean Difference (IV, Fixed, 95% CI)

‐0.89 [‐2.70, 0.93]

2.2 Cilazapril 2.5 mg

12

697

Mean Difference (IV, Fixed, 95% CI)

‐3.15 [‐4.29, 0.00]

2.3 Enalapril 10 mg

8

1138

Mean Difference (IV, Fixed, 95% CI)

‐3.11 [‐2.00, ‐2.23]

2.4 Fosinopril 10 mg

3

239

Mean Difference (IV, Fixed, 95% CI)

‐3.42 [‐5.43, ‐1.42]

2.5 Imidapril 5 mg

1

68

Mean Difference (IV, Fixed, 95% CI)

‐3.2 [‐7.41, 1.01]

2.6 Lisinopril 20 mg

1

80

Mean Difference (IV, Fixed, 95% CI)

‐4.6 [‐8.63, ‐0.57]

2.7 Moexipril 7.5 mg

3

223

Mean Difference (IV, Fixed, 95% CI)

‐2.18 [‐4.11, ‐0.24]

2.8 Perindopril 2 mg

2

134

Mean Difference (IV, Fixed, 95% CI)

‐2.31 [‐5.06, 0.45]

2.9 Ramipril 5 mg

4

291

Mean Difference (IV, Fixed, 95% CI)

‐3.65 [‐5.62, ‐1.67]

2.10 Spirapril 3 mg

2

184

Mean Difference (IV, Fixed, 95% CI)

‐4.20 [‐6.66, ‐1.74]

2.11 Trandolapril 1 mg

4

390

Mean Difference (IV, Fixed, 95% CI)

‐3.52 [‐4.92, ‐2.11]
Figuras y tablas -
Comparison 17. 1/4 Max Dose vs Placebo
Ir a la tabla de la revisión
Comparison 18. 1/2 Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

51

4980

Mean Difference (IV, Fixed, 95% CI)

‐7.60 [‐8.40, ‐6.79]

1.1 Benazepril 20 mg

6

504

Mean Difference (IV, Fixed, 95% CI)

‐7.97 [‐10.41, ‐5.52]

1.2 Cilazapril 5 mg

5

379

Mean Difference (IV, Fixed, 95% CI)

‐5.92 [‐8.70, ‐3.14]

1.3 Enalapril 20 mg

8

967

Mean Difference (IV, Fixed, 95% CI)

‐9.54 [‐11.22, ‐7.86]

1.4 Fosinopril 20 mg

5

277

Mean Difference (IV, Fixed, 95% CI)

‐8.99 [‐12.35, ‐5.62]

1.5 Imidapril 10 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐8.90 [‐16.26, ‐1.54]

1.6 Lisinopril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.7 Moexipril 15 mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐8.02 [‐11.16, ‐4.88]

1.8 Perindopril 4 mg

6

868

Mean Difference (IV, Fixed, 95% CI)

‐6.53 [‐9.04, ‐4.02]

1.9 Quinapril 20 mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐7.05 [‐11.26, ‐2.84]

1.10 Ramipril 10 mg

4

344

Mean Difference (IV, Fixed, 95% CI)

‐6.17 [‐9.07, ‐3.27]

1.11 Spirapril 6 mg

3

303

Mean Difference (IV, Fixed, 95% CI)

‐7.43 [‐10.41, ‐4.46]

1.12 Trandolapril 2 mg

7

769

Mean Difference (IV, Fixed, 95% CI)

‐6.17 [‐8.24, ‐4.10]

2 Change in trough DBP Show forest plot

57

5623

Mean Difference (IV, Fixed, 95% CI)

‐4.67 [‐5.09, ‐4.25]

2.1 Benazepril 20 mg

6

504

Mean Difference (IV, Fixed, 95% CI)

‐4.30 [‐5.70, ‐2.90]

2.2 Cilazapril 5 mg

9

800

Mean Difference (IV, Fixed, 95% CI)

‐3.40 [‐4.45, ‐2.36]

2.3 Enalapril 20 mg

9

1039

Mean Difference (IV, Fixed, 95% CI)

‐5.29 [‐6.22, ‐4.37]

2.4 Fosinopril 20 mg

5

277

Mean Difference (IV, Fixed, 95% CI)

‐6.86 [‐8.70, ‐5.02]

2.5 Imidapril 10 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐7.40 [‐12.13, ‐2.67]

2.6 Lisinopril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.7 Moexipril 15 mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐4.26 [‐5.93, ‐2.60]

2.8 Perindopril 4 mg

6

868

Mean Difference (IV, Fixed, 95% CI)

‐4.81 [‐6.04, ‐3.58]

2.9 Quinapril 20 mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐3.35 [‐5.98, ‐0.72]

2.10 Ramipril 10 mg

4

344

Mean Difference (IV, Fixed, 95% CI)

‐4.47 [‐6.17, ‐2.76]

2.11 Spirapril 6 mg

4

453

Mean Difference (IV, Fixed, 95% CI)

‐5.92 [‐7.45, ‐4.39]

2.12 Trandolapril 2 mg

7

769

Mean Difference (IV, Fixed, 95% CI)

‐4.24 [‐5.35, ‐3.14]
Figuras y tablas -
Comparison 18. 1/2 Max Dose vs Placebo
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Comparison 19. Max Dose vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

16

1450

Mean Difference (IV, Fixed, 95% CI)

‐8.48 [‐9.91, ‐7.06]

1.1 Benazepril 40 mg

2

112

Mean Difference (IV, Fixed, 95% CI)

‐8.67 [‐13.73, ‐3.62]

1.2 Cilazapril 10 mg

1

101

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐11.99, ‐2.01]

1.3 Enalapril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.4 Fosinopril 40 mg

3

245

Mean Difference (IV, Fixed, 95% CI)

‐7.78 [‐11.20, ‐4.36]

1.5 Imidapril 20 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐12.90 [‐20.56, ‐5.24]

1.6 Lisinopril 80 mg

1

79

Mean Difference (IV, Fixed, 95% CI)

‐13.8 [‐20.77, ‐6.83]

1.7 Moexipril 30 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.8 Perindopril 8 mg

2

129

Mean Difference (IV, Fixed, 95% CI)

‐10.09 [‐16.14, ‐4.05]

1.9 Quinapril 40 mg

1

14

Mean Difference (IV, Fixed, 95% CI)

‐6.0 [‐20.16, 8.16]

1.10 Ramipril 20 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.11 Spirapril 12 mg

2

226

Mean Difference (IV, Fixed, 95% CI)

‐8.23 [‐11.65, ‐4.82]

1.12 Trandolapril 4 mg

3

478

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐10.41, ‐5.59]

2 Change in trough DBP Show forest plot

17

1636

Mean Difference (IV, Fixed, 95% CI)

‐4.95 [‐5.71, ‐4.20]

2.1 Benazepril 40 mg

2

112

Mean Difference (IV, Fixed, 95% CI)

‐4.76 [‐7.84, ‐1.69]

2.2 Cilazapril 10 mg

2

287

Mean Difference (IV, Fixed, 95% CI)

‐4.06 [‐5.74, ‐2.37]

2.3 Enalapril 40 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 Fosinopril 40 mg

3

245

Mean Difference (IV, Fixed, 95% CI)

‐4.63 [‐6.61, ‐2.65]

2.5 Imidapril 20 mg

1

66

Mean Difference (IV, Fixed, 95% CI)

‐6.3 [‐10.88, ‐1.72]

2.6 Lisinopril 80 mg

1

79

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐9.96, ‐2.04]

2.7 Moexipril 30 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.8 Perindopril 8 mg

2

129

Mean Difference (IV, Fixed, 95% CI)

‐5.94 [‐8.81, ‐3.07]

2.9 Quinapril 40 mg

1

14

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐17.78, ‐0.22]

2.10 Ramipril 20 mg

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.11 Spirapril 12 mg

2

226

Mean Difference (IV, Fixed, 95% CI)

‐6.02 [‐8.09, ‐3.96]

2.12 Trandolapril 4 mg

3

478

Mean Difference (IV, Fixed, 95% CI)

‐4.71 [‐6.05, ‐3.37]
Figuras y tablas -
Comparison 19. Max Dose vs Placebo
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Comparison 20. 2 Max and Higher Doses vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

7

738

Mean Difference (IV, Fixed, 95% CI)

‐8.81 [‐10.92, ‐6.70]

1.1 Benazepril 80 mg

1

77

Mean Difference (IV, Fixed, 95% CI)

‐11.40 [‐17.51, ‐5.29]

1.2 Imidapril 40 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐10.60 [‐17.40, ‐3.80]

1.3 Perindopril 16 mg

1

108

Mean Difference (IV, Fixed, 95% CI)

‐8.9 [‐15.36, ‐2.44]

1.4 Spirapril 24 mg

2

220

Mean Difference (IV, Fixed, 95% CI)

‐9.40 [‐12.67, ‐6.12]

1.5 Trandolapril 8, 12, 16 mg

2

266

Mean Difference (IV, Fixed, 95% CI)

‐6.03 [‐10.14, ‐1.93]

2 Change in trough DBP Show forest plot

7

738

Mean Difference (IV, Fixed, 95% CI)

‐5.25 [‐6.45, ‐4.05]

2.1 Benazepril 80 mg

1

77

Mean Difference (IV, Fixed, 95% CI)

‐6.80 [‐10.34, ‐3.26]

2.2 Imidapril 40 mg

1

67

Mean Difference (IV, Fixed, 95% CI)

‐6.5 [‐11.22, ‐1.78]

2.3 Perindopril 16 mg

1

108

Mean Difference (IV, Fixed, 95% CI)

‐5.5 [‐8.48, ‐2.52]

2.4 Spirapril 24 mg

2

220

Mean Difference (IV, Fixed, 95% CI)

‐4.56 [‐6.66, ‐2.47]

2.5 Trandolapril 8, 12, 16 mg

2

266

Mean Difference (IV, Fixed, 95% CI)

‐5.02 [‐7.12, ‐2.93]
Figuras y tablas -
Comparison 20. 2 Max and Higher Doses vs Placebo
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Comparison 21. 1/2 Max and Higher Doses vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in trough SBP Show forest plot

53

6113

Mean Difference (IV, Fixed, 95% CI)

‐7.85 [‐8.60, ‐7.09]

1.1 Benazepril 20, 40, 80 mg

6

598

Mean Difference (IV, Fixed, 95% CI)

‐8.54 [‐10.87, ‐6.21]

1.2 Cilazapril 5, 10 mg

5

429

Mean Difference (IV, Fixed, 95% CI)

‐5.79 [‐8.46, ‐3.12]

1.3 Enalapril 20, (40) mg

8

967

Mean Difference (IV, Fixed, 95% CI)

‐9.54 [‐11.22, ‐7.86]

1.4 Fosinopril 20, 40 mg

4

359

Mean Difference (IV, Fixed, 95% CI)

‐7.44 [‐10.44, ‐4.44]

1.5 Imidapril 10, 20, 40 mg

1

129

Mean Difference (IV, Fixed, 95% CI)

‐10.8 [‐16.60, ‐5.00]

1.6 Lisinopril (40), 80 mg

1

50

Mean Difference (IV, Fixed, 95% CI)

‐13.8 [‐24.46, ‐3.14]

1.7 Moexipril 15, (30) mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐8.02 [‐11.16, ‐4.88]

1.8 Perindopril 4, 8, 16 mg

6

985

Mean Difference (IV, Fixed, 95% CI)

‐7.12 [‐9.55, ‐4.70]

1.9 Quinapril 20, (40) mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐7.05 [‐11.26, ‐2.84]

1.10 Ramipril 10, (20) mg

4

257

Mean Difference (IV, Fixed, 95% CI)

‐5.74 [‐9.33, ‐2.16]

1.11 Spirapril 6, 12, 24 mg

3

521

Mean Difference (IV, Fixed, 95% CI)

‐8.31 [‐10.80, ‐5.82]

1.12 Trandolapril 2, 4, 8, 12, 16 mg

9

1315

Mean Difference (IV, Fixed, 95% CI)

‐7.02 [‐8.70, ‐5.34]

2 Change in trough DBP Show forest plot

59

6861

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐5.13, ‐4.34]

2.1 Benazepril 20, 40, 80 mg

6

598

Mean Difference (IV, Fixed, 95% CI)

‐4.56 [‐5.91, ‐3.22]

2.2 Cilazapril 5, 10 mg

9

942

Mean Difference (IV, Fixed, 95% CI)

‐3.58 [‐4.57, ‐2.60]

2.3 Enalapril 20, (40) mg

9

1039

Mean Difference (IV, Fixed, 95% CI)

‐5.29 [‐6.22, ‐4.37]

2.4 Fosinopril 20, 40 mg

4

359

Mean Difference (IV, Fixed, 95% CI)

‐5.15 [‐6.85, ‐3.45]

2.5 Imidapril 10, 20, 40 mg

1

129

Mean Difference (IV, Fixed, 95% CI)

‐6.7 [‐10.54, ‐2.86]

2.6 Lisinopril (40), 80 mg

1

79

Mean Difference (IV, Fixed, 95% CI)

‐6.00 [‐9.96, ‐2.04]

2.7 Moexipril 15, (30) mg

4

321

Mean Difference (IV, Fixed, 95% CI)

‐4.26 [‐5.93, ‐2.60]

2.8 Perindopril 4, 8, 16 mg

6

985

Mean Difference (IV, Fixed, 95% CI)

‐5.01 [‐6.18, ‐3.84]

2.9 Quinapril 20, (40) mg

2

182

Mean Difference (IV, Fixed, 95% CI)

‐3.35 [‐5.98, ‐0.72]

2.10 Ramipril 10, (20) mg

4

257

Mean Difference (IV, Fixed, 95% CI)

‐4.42 [‐6.55, ‐2.29]

2.11 Spirapril 6, 12, 24 mg

4

671

Mean Difference (IV, Fixed, 95% CI)

‐5.84 [‐7.19, ‐4.49]

2.12 Trandolapril 2, 4, 8, 12, 16 mg

9

1299

Mean Difference (IV, Fixed, 95% CI)

‐4.65 [‐5.55, ‐3.74]
Figuras y tablas -
Comparison 21. 1/2 Max and Higher Doses vs Placebo
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Comparison 22. ACE Inhibitors vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Change in peak SBP [1/2 Max and Higher Doses Only] Show forest plot

11

1154

Mean Difference (IV, Fixed, 95% CI)

‐11.53 [‐13.27, ‐9.78]

1.1 1/2 Max Dose

11

783

Mean Difference (IV, Fixed, 95% CI)

‐11.06 [‐13.11, ‐9.02]

1.2 Max Dose

3

143

Mean Difference (IV, Fixed, 95% CI)

‐11.48 [‐17.37, ‐5.60]

1.3 2 Max Dose

3

228

Mean Difference (IV, Fixed, 95% CI)

‐13.36 [‐17.40, ‐9.31]

2 Change in peak DBP [1/2 Max and Higher Doses Only] Show forest plot

15

1485

Mean Difference (IV, Fixed, 95% CI)

‐6.37 [‐7.15, ‐5.58]

2.1 1/2 Max Dose

15

1103

Mean Difference (IV, Fixed, 95% CI)

‐6.02 [‐6.95, ‐5.08]

2.2 Max Dose

4

157

Mean Difference (IV, Fixed, 95% CI)

‐6.49 [‐8.81, ‐4.16]

2.3 2 Max Dose

3

225

Mean Difference (IV, Fixed, 95% CI)

‐7.69 [‐9.56, ‐5.82]

3 Change in peak SBP [All Doses] Show forest plot

11

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 1/8 Max Dose

1

11

Mean Difference (IV, Fixed, 95% CI)

‐11.3 [‐30.46, 7.86]

3.2 1/4 Max Dose

6

326

Mean Difference (IV, Fixed, 95% CI)

‐6.03 [‐9.93, ‐2.13]

3.3 1/2 Max Dose

11

724

Mean Difference (IV, Fixed, 95% CI)

‐10.97 [‐13.14, ‐8.80]

3.4 Max Dose

3

136

Mean Difference (IV, Fixed, 95% CI)

‐11.43 [‐17.69, ‐5.16]

3.5 2 Max Dose

3

211

Mean Difference (IV, Fixed, 95% CI)

‐13.58 [‐18.03, ‐9.13]

4 Change in peak DBP [All Doses] Show forest plot

15

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 1/8 Max Dose

3

154

Mean Difference (IV, Fixed, 95% CI)

‐9.51 [‐12.64, ‐6.38]

4.2 1/4 Max Dose

9

451

Mean Difference (IV, Fixed, 95% CI)

‐3.69 [‐5.24, ‐2.15]

4.3 1/2 Max Dose

15

981

Mean Difference (IV, Fixed, 95% CI)

‐5.98 [‐7.02, ‐4.94]

4.4 Max Dose

4

157

Mean Difference (IV, Fixed, 95% CI)

‐6.49 [‐8.81, ‐4.16]

4.5 2 Max Dose

3

212

Mean Difference (IV, Fixed, 95% CI)

‐7.78 [‐9.74, ‐5.83]

5 Change in trough heart rate Show forest plot

16

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

5.1 1/8 Max Dose

1

114

Mean Difference (IV, Fixed, 95% CI)

‐3.0 [‐6.62, 0.62]

5.2 1/4 Max Dose

10

587

Mean Difference (IV, Fixed, 95% CI)

‐0.47 [‐1.76, 0.81]

5.3 1/2 Max Dose

9

917

Mean Difference (IV, Fixed, 95% CI)

‐0.71 [‐1.99, 0.57]

5.4 Max Dose

2

89

Mean Difference (IV, Fixed, 95% CI)

1.31 [‐2.15, 4.76]

6 Total withdrawals due to adverse effects Show forest plot

56

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 1/16 Max Dose

4

282

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.39, 2.57]

6.2 1/8 Max Dose

9

842

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.42, 1.82]

6.3 1/4 Max Dose

32

3385

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.42, 1.00]

6.4 1/2 Max Dose

38

3568

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.55, 1.19]

6.5 Max Dose

8

840

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.56, 2.35]

6.6 2 Max Dose

5

567

Risk Ratio (M‐H, Fixed, 95% CI)

1.51 [0.68, 3.34]
Figuras y tablas -
Comparison 22. ACE Inhibitors vs Placebo
Ir a la tabla de la revisión