Suspensión de fármacos antihipertensivos en personas mayores
Referencias
Referencias de los estudios incluidos en esta revisión
Referencias de los estudios excluidos de esta revisión
Referencias adicionales
Referencias de otras versiones publicadas de esta revisión
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Ir a:
| Study characteristics | ||
| Methods | Study design: Randomised controlled trial Study grouping: Parallel group | |
| Participants | Number of participants randomised (discontinuation/continuation): 54/52 Baseline Characteristics Stop
Continue
Overall
Included criteria: On a long‐stay geriatric ward. Prescribed a diuretic for more than 1 month. The consultant physicians agreed that there was no reason to believe that diuretic administration was mandatory. Excluded criteria: If discontinuation of the treatment might be unsafe as defined by the following criteria: 1. They had had congestive cardiac failure during the previous three months; 2. They had ever had left ventricular failure; 3. They had hypertension which had been controlled in hospital by diuretic therapy; 4. They were receiving diuretics for a nephrotic syndrome or glaucoma. Pretreatment: No detailed information on patient characteristics provided. Based on description in text and Table II, groups were balanced according to specific medication use and sex. But discontinuation group slightly younger (mean age 82.4 years for continuation versus 81.6 years for discontinuation group) and lower BP and heart rate at baseline Withdrawal (from study) criteria: Death due to unrelated causes; diuretics considered necessary: congestive cardiac failure, left ventricular failure, increasing dyspnoea and oedema, tight calliper due to oedema, cellulitis of leg, oedema after leg injury, atrial fibrillation, bronchopneumonia; diuretics considered undesirable owing to difficulty in swallowing and dehydration Process of drug withdrawal (tapering): Not specified Antihypertensives taken: Frusemide, frusemide and spironolactone, amiloride‐hydrocholorthiazide combination, frusemide and amiloride‐hydrocholorthiazide combination, cyclopentiazide‐potassium chloride combination, clopamide, chlorthalidone | |
| Interventions | Intervention Characteristics Stop Continue | |
| Outcomes | Systolic blood pressure
Diastolic blood pressure
Increase in oedema
Decrease in oedema
Plasma potassium level
Urea level
Mortality
| |
| Identification | Sponsorship source: No sponsor listed. The following pharmaceutical manufacturers supplied the active and placebo tablets: CIBA Laboratories, Geigy Pharmaceuticals Ltd, Hoechst Pharmaceuti‐cals Ltd, Merck Sharp & Dohme Ltd, Sandoz Products Ltd, and Searle Laboratories Country: Cardiff, Wales Setting: Long‐stay geriatric wards (x 6) Authors name: M.L. Burr Institution: M.R.C. Epidemiology Unit, Cardiff, Gwent Geriatric Service, Newport and University Hospital of Wales, Cardiff Email: None provided Address: None provided | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "... randomly allocated into two groups." Judgement comment: not enough information to make judgement |
| Allocation concealment (selection bias) | Unclear risk | Quote: "... allocated into two groups." Judgement comment: not enough information to make judgement |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "... tablets of similar appearance. Potassium supplements were similarly replaced by placebo tablets for patients allocated to the placebo group. The active and placebo tablets were supplied individually in special containers, so that the medical and nursing staff were unaware of the group to which each patient was assigned." Judgement comment: based on results in table IV, appeared that blinding was generally effective |
| Blinding of outcome assessment (detection bias) | High risk | Quote: "The patients were observed by the consultants or their deputies for signs of cardiac failure, especially during the first two weeks of the trial, so that diuretic therapy could be resumed if it was judged to be necessary. Plasma electrolyte estimations were performed before each patient entered the trial and repeated after four weeks and again after twelve weeks. Repeated observations of blood pressure, ankle oedema and general condition were made before and during the trial by the same nurse (S.K.)." Judgement comment: not stated that assessors were blinded. As all observations done by same nurse, they would have seen BP results which could have biased their assessment of other factors |
| Incomplete outcome data (attrition bias) | High risk | Quote: "The other 89 patients completed 12 weeks in the trial and are the subjects of the remaining tables." Judgement comment: results are reported only for those that completed the trial and not all enrolled. Table 3 shows uneven exclusions from the trial between active and placebo with higher dropout rate in placebo group and per protocol analysis. |
| Selective reporting (reporting bias) | Unclear risk | Judgement comment: primary and secondary outcomes were not reported in the methods. A number of outcome results were reported but we weren't able to know if these were planned outcomes and if any were not reported. Most outcomes described in methods were reported in results; however, there was no detailed description for some outcomes. |
| Other bias | Low risk | Judgement comment: no other areas of concern |
| Study characteristics | ||
| Methods | Study design: Randomised controlled trial Study grouping: Parallel group | |
| Participants | Number of participants randomised (discontinuation/continuation): 159/81 Baseline Characteristics Obese: continue (no dietary interventions)
Obese: discontinue medication (no dietary interventions)
Not obese: continue (no dietary interventions)
Not obese: discontinue medication (no dietary interventions)
Included criteria: Participants were enrolled in the current programme (DISH: Dietary intervention Study of Hypertension) if they were previously active stepped care HDFP participants (at one of 3 centres (Jackson, Birmingham or NY)). Persons were eligible for participation in DISH if they: (1) had no systolic blood pressure > 180 mmHg recorded during the previous year; (2) the average of the diastolic blood pressure was < 95 mmHg during the past year; and (3) the average of the last two diastolic blood pressure readings was greater than or equal to 90 mmHg, and neither > 95 mmHg. Age 30‐69. receiving antihypertensive for past 5 years, hypertension well controlled Excluded criteria: Participants were excluded if they had a history of congestive heart failure, history or ECG evidence of myocardial infarction, history of stroke or transient ischaemic attacks, serum creatinine concentration > 2.5 mg/100 mL on at least two determinations, history of personal, social or psychological problems, or an intercurrent illness making compliance with the protocol dietary regimens difficult or impossible, or severe alcoholism, intercurrent pregnancy, beta‐blocker therapy for angina, or glucocorticoid therapy for an indefinite period of time. Pretreatment: There were modest examples of inhomogeneity of randomisation, as anticipated, with these relatively small groups. However, none of these were considered by study authors to be significant enough to affect analysis. Withdrawal criteria (criteria for restarting medication): Medication was restarted if (a) the diastolic blood pressure reached 95 ‐ 99 mmHg on three occasions within a three‐month period; (b) if two diastolic blood pressures were in the 100 ‐ 104 mmHg range during a one‐month period; (c) if any time diastolic blood pressure rose to 105 mmHg or higher. If a participant's medication was restarted due to blood pressure rise as specified or if medication was restarted by physicians outside the study, this was considered a terminating event and the participant was counted as a withdrawal failure. Other occurrences defined as terminating events included stroke, new myocardial infarction, congestive heart failure, or elevated creatinine. Patients were considered a continuing success if medication had not been restarted for any of the above reasons and they had not had a terminating event at the time of analysis. Group randomisation: Participants were initially grouped into those individuals who were 120% or more than ideal weight (obese) and those who weighed less (non‐obese). The obese participants were randomised into four groups: (1) continue medication; (2) discontinue medication, no dietary intervention; (3) discontinue medication, weight loss; (4) discontinue medication, decrease sodium intake. The non‐obese participants were randomised to three groups: (1) continue medication; (2) discontinue medications, no dietary intervention; (3) discontinue medication, sodium restriction. Process of drug withdrawal (tapering): Participants randomised to discontinue drugs were withdrawn from therapy using a standardised step‐down withdrawal programme taking from 2 to 8 weeks, depending on the number and dosage of drugs at entry. The diuretic was the last agent withdrawn. Drug withdrawal took place in a stepped fashion with the highest step drug being removed first. Target time for withdrawal was 6 weeks. Antihypertensives taken: At the baseline visit, of the obese non‐intervention group, 34% had their hypertension under control with diuretics alone (Hypertension Detection Follow‐Up Program Step 1 drugs); another 37% were under control with diuretics plus either reserpine or methyldopa (Step 2); the remaining 29% were additionally on hydralazine (Step 3) and guanethedine (Step 4) and on other antihypertensive drugs (Step 5). Among those in the non‐obese non‐intervention group at baseline, 31% were on diuretics alone and another 29% were on diuretics plus reserpine or methyldopa. The remaining 40% were on Step 3, 4 or 5 drugs. | |
| Interventions | Intervention Characteristics Obese: continue Obese: discontinue medication (no dietary interventions) Not obese: continue Not obese: discontinue medication (no dietary interventions) | |
| Outcomes | Percentage remaining off antihypertensive medications
| |
| Identification | Sponsorship source: Grant R01 HL24369, with the National Heart, Lung and Blood Institute, NIH, Department of Health and Human Services. Drugs were supplied for this study by the following companies: Inderal, Ayerst Laboratories; Aldomet, Merck Sharp and Dohme; Apresoline and Ismelin, Ciba‐Geigy Corp.; Catapres, Boehringer Ingelheim Ltd.; Hygroton and Rergoton, USV Pharmaceutical Corp.; Aldactone, Searle Laboratories Country: USA Setting: Primary care (community) Authors name: Herbert G. Langford Institution: Departments of Medicine, University of Mississippi Medical Center Email: None provided Address: Departments of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, US | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "The 584 eligible patients as shown in Fig 1 were stratified by clinical center and by obesity and randomized before requesting consent to one of the following seven groups..." Judgement comment: not enough information to make judgement |
| Allocation concealment (selection bias) | Unclear risk | Judgement comment: not enough information to make judgement |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "... among these groups (Table 4); 23% of all failures were due to private (non‐ study) physicians' restarting therapy with antihypertensive medication, at least on some occasions despite continued normotension." Judgement comment: manuscripts did not specify if blinded. High possibility that they were not blinded (no mention of placebo tablets, plus, as there were dietary interventions in the other groups, this would not have been able to be blinded). Additionally, this quote would indicate that they weren't blinded. Outcomes were susceptible to bias due to participant and personnel lack of blinding. |
| Blinding of outcome assessment (detection bias) | High risk | Judgement comment: outcome of restarting antihypertensive medication was based on objective criteria related to BP readings though drug therapy could be restarted by physicians outside the study (private physician restart was reason for restart in around 25% of restarts in overweight group and 32% in non‐overweight). The decision to restart could be influenced by knowledge of group. |
| Incomplete outcome data (attrition bias) | Unclear risk | Judgement comment: reported outcomes for participants in discontinuation groups, but not all outcomes in continuation group. No clear details on dropouts (particularly in continuation group) |
| Selective reporting (reporting bias) | High risk | Judgement comment: multiple papers published on this study, presenting results and different subgroup analyses which raises concern regarding selective reporting of results; based on methods in main paper, BP was measured at study visits though this does not appear to be reported. |
| Other bias | Low risk | Judgement comment: no other areas of concern |
| Study characteristics | ||
| Methods | Study design: Randomised controlled trial Study grouping: Parallel group | |
| Participants | Number of participants randomised (discontinuation/continuation): 31/31 Baseline Characteristics Stop
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Overall
Included criteria: An average DBP of 90 mmHg or less at an eligibility visit plus the two preceding visits. No DBP above 95 mm Hg at any of the above 3 visits. An average DBP of 90 mm Hg or less for all visits during the preceding 12 months. Only antihypertensive medication used during the preceding 12 months was a diuretic. Excluded criteria: History of major cardiovascular events, such as stroke, myocardial infarction, transient ischaemic attack, congestive heart failure, renal failure, and severe angina pectoris. Evidence by valid count of unused medication on more than two occasions during the preceding 12 months, of less than 80% or more than 110% of prescribed usage. Inability or unwillingness to attend clinic at least once every 4 to 6 weeks. Pretreatment: The following characteristics were measured: gender, race, age, mean BP, mean pretrial BP, pre‐HDFP (Hypertension Detection and Follow‐up Program), history of hypertension, antihypertensive treatment at HDFP intake. Differences not explicitly stated in the text. As per Table 2, there were more males than females in active (continuation) versus placebo (stop) group; mean age similar in both groups. BP measures were similar across groups. Removal criteria: Any one visit with an average DBP of 105 mmHg or higher; any 2 visits with an average DBP of 96‐104 mmHg; any 5 visits with an average DBP above 90 mmHg; an average DBP above 90 mmHg for all visits at the end of the first 24 weeks Process of drug withdrawal (tapering): Not specified Antihypertensives taken: Of 62 enrolled subjects, 54 (87%) were taking chlorthalidone, 7 (11%) were taking hydrochlorothiazide, and 1 (2%) was taking triamterene. All pretrial regimens had been in use for at least 12 months of the HDFP. None of the participants in the trial was taking potassium supplement, uricosuric drugs, or allopurinol. | |
| Interventions | Intervention Characteristics Stop Continue | |
| Outcomes | Reversions (restarted pretrial medication due to BP)
Systolic BP change (mean BP of last 2 trial visits minus pretrial BP)
Diastolic BP change (mean BP of last 2 trial visits minus pretrial BP)
Systolic BP
Mortality
Stroke (fatal and non‐fatal, ischaemic and haemorrhagic, transient ischaemic attack)
MI
| |
| Identification | Sponsorship source: Supported in part by a grant from the Montana State Heart Association. The United States Vitamin Corporation and Abbott Laboratories generously supplied the active and placebo dosage forms used in this study. Country: USA Setting: Community setting Comments: A follow‐on study on a subset of participants from the National Hypertension Detection and Follow‐up Program (HDFP) ‐ those from the Salt Lake City Clinical Centre Authors name: Lynn J. Maland Institution: Department of Family and Community Medicine, University of Utah, Salt Lake City, Utah Email: Not stated Address: Dr Lawrence J Lutz, MD, MSCM, Department of Family and Community Medicine, University of Utah, Salt Lake City, Utak 84132 | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "... were randomly assigned in a double‐blind manner." Judgement comment: not enough information to make judgement |
| Allocation concealment (selection bias) | Unclear risk | Judgement comment: not enough information to make judgement |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "... double‐ blind manner to receive either the same diuretic they had been taking at the end of the HDFP, or a physically identical placebo." Judgement comment: noted to be 'double‐blind', physically identical placebo used |
| Blinding of outcome assessment (detection bias) | Unclear risk | Quote: "... two each using a standard and a random zero mercury manometer (Hawksley, England) and an appropriately sized cuff. The random zero device conceals the true zero point of the mercury column until the reading is completed to avoid digit preferences in BP readings." "The average of the two random zero measurements (the 2nd and 4th) was taken as the official reading for each visit. The diastolic pressure was read as the 5th phase of the Korotkov sounds." Judgement comment: the study was said to be 'double‐blind' but no further information. This method was intended to remove digit bias in assessors, but not necessarily related to blinding. |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "Fifty‐nine of the original 62 enrollees completed the 1‐year follow‐up. The three who did not complete the study included one patient in the active treatment group who died from cardiac arrest, and two dropouts from the placebo group." Judgement comment: small total number of dropouts ‐ different reasons for dropout between groups, but as such small number unable to determine if due to treatment. One in each group had a cardiac event which led to their dropout (one due to death). |
| Selective reporting (reporting bias) | High risk | Judgement comment: all stated outcomes in the methods were reported ‐ but the manner in which they were reported was unclear. BP results were given with reverters as a separate group (i.e. not randomised group). Adverse drug reactions mentioned but full details not given. Also unclear whether other outcomes not mentioned in the manuscript |
| Other bias | Low risk | Judgement comment: no other areas of concern |
| Study characteristics | ||
| Methods | Study design: Randomised controlled trial Study grouping: Parallel group | |
| Participants | Number of participants randomised (discontinuation/continuation): 199/186 Baseline Characteristics Stop
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Overall
Included criteria: 75 years or older, used antihypertensive treatment, systolic BP of 160 mmHg or less, and a Mini‐Mental State Examination (MMSE) score of 21 to 27. Persons with a history of peripheral arterial disease, myocardial infarction, or a coronary reperfusion procedure or persons with diabetes mellitus could participate if their SBP was 140 mmHg or less. Excluded criteria: A clinical diagnosis of dementia, use of antihypertensives for reasons other than hypertension, current angina pectoris, cardiac arrhythmia, heart failure, myocardial infarction or a coronary reperfusion procedure less than 3 years ago, a history of stroke or transient ischaemic attack, a limited life expectancy Pretreatment: Baseline characteristics of both groups were well balanced except for a slight imbalance in the use of β‐blockers and in Trail Making Test Δ scores. Removal criteria: During the 6‐16‐week period after randomisation, the physician was instructed to restart antihypertensive treatment for safety reasons when measurements of BP at the home visit showed a diastolic BP of 120 mmHg or greater, an SBP of 200 mmHg or greater (180 mmHg for participants with diabetes mellitus or those who had had a cardiovascular event > 3 years ago), or an increase in SBP of 60 mmHg or greater relative to baseline. Antihypertensives taken: Intervention (discontinuation)/Control (continuation): β‐Blocker 64 (35.6)/75 (42.6); diuretic 99 (55.0)/92 (52.3); angiotensin‐converting enzyme inhibitor 60 (33.3)/61 (34.7); angiotensin receptor blocker 60 (33.3)/63 (35.8); calcium channel blocker 40 (22.2)/40 (22.7); ≥ 2 agents 109 (60.6)/110 (62.5) Process of withdrawal: The discontinuation of antihypertensive treatment was performed by the participant’s physician according to an algorithm composed by the investigators (outlined in Supplement 2). All physicians were instructed to withdraw antihypertensive treatment until a maximum increase of 20 mmHg in SBP was reached. During this phase, the physician monitored BP every week until no further changes in antihypertensive treatment were made. | |
| Interventions | Intervention Characteristics Stop Continue | |
| Outcomes | Systolic BP change (ITT)
Diastolic BP change (ITT)
Mortality
Stroke
MI
QOL
TIA
Hospitalisations (total)
| |
| Identification | Sponsorship source: This work was supported by a grant from the Netherlands Organization for Health Research and Development (ZonMw), Program Priority Medicines for the Elderly (grant no: 40‐41600‐98‐9014). This funding source had no role in the study design, the collection, analysis and interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication. All researchers worked independently from the funding source. Country: Netherlands Setting: Community‐based; across 128 general practices Authors name: Justine E. F. Moonen Institution: Department of Psychiatry, Leiden University Medical Centre Email: [email protected] Address: Department of Psychiatry, Leiden University Medical Center, PO Box 10392, 2300 WB, Leiden, the Netherlands | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Participants were randomly assigned, in a 1:1 ratio, to parallel discontinuation (intervention group) or continuation (control group) of antihypertensive treatment (Figure 1). Stratified block randomization was used (with block sizes of 4 per general practice) to ensure that intervention and control participants were equally distributed within general practices." Judgement comment: a computerised randomisation procedure was used. |
| Allocation concealment (selection bias) | Low risk | Quote: "Concealment of treatment allocation was ensured by a central computerized randomization procedure." Judgement comment: concealment of treatment allocation was ensured by a central computerised randomisation procedure. |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "Participants and the physicians conducting the intervention were not masked to the allocated intervention." Judgement comment: participants and the physicians conducting the intervention were not blinded. Many of the outcomes (or reporting of outcomes) may have been susceptible to bias due to knowledge of the intervention. |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "Study outcomes and MRIs were assessed in a standardized manner by research personnel ... masked to the allocated intervention." Judgement comment: paper stated that study outcomes and MRIs were assessed in a standardised manner by research personnel masked to the allocated intervention. |
| Incomplete outcome data (attrition bias) | Low risk | Quote: "Furthermore, 19 participants in the intervention group and 10 in the control group had no follow‐up measurement." Judgement comment: a per‐protocol analysis was performed. Reason for missing data was unlikely to be related to the true outcome of this study. |
| Selective reporting (reporting bias) | High risk | Judgement comment: study protocol (provided as supplementary material) noted that Neuropsychiatric Inventory (NPI) would be carried out for, among others, assessment of depression and apathy. This outcome was not reported. |
| Other bias | Low risk | Judgement comment: no other areas of concern |
| Study characteristics | ||
| Methods | Study design: Randomised controlled trial Study grouping: Parallel group Stratification of randomisation: The randomisation process included stratification for the presence of heart disease and/or hypertension. Study was double‐blind. | |
| Participants | Number of participants randomised (discontinuation/continuation): 38/39 Baseline Characteristics Stop (placebo)
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Overall
Included criteria: Resident of geriatric institution. Taking one or more diuretics (hydrochlorothiazide, frusemide, spironolactone, hydrochlorothiazide and spironolactone, hydrochlorothiazide and triamterene). 60 years and over Excluded criteria: Concurrent digoxin use; individuals with clinical or radiological evidence of heart failure; residents with hypertension (blood pressure requiring nondiuretic antihypertensive therapy or a level above 160 mmHg systolic and/or 105 mmHg diastolic while receiving diuretics); on diuretic therapy less than 3 months; uncooperative/no consent; terminal illness unrelated to diuretic. Pretreatment: The mean daily dose of diuretic was slightly higher in the diuretic group at baseline but this difference was not present at 12 months. Mean baseline blood pressures in the supine position were similar in the two groups. Sitting and erect values were slightly higher in the placebo subjects, whereas initial postural blood pressure changes were more marked in the diuretic group. The mean heart rates of the two groups were similar. Withdrawal criteria: Heart failure or clinically significant hypertension: the presence or absence of heart failure was determined by the physician according to criteria used in the Framingham Study. Clinically important hypertension was defined as a blood pressure above 180 mmHg systolic and 110 mmHg diastolic on two consecutive visits at least one week apart. Process of drug withdrawal (tapering): Not specified Antihypertensives taken: hydrochlorothiazide ‐ 18/14 (continue/stop); frusemide ‐ 17/20; spironolactone ‐ 4/0; hydrochlorothiazide and spironolactone ‐ 5/2; hydrochlorothiazide and triamterene ‐ 3/4 | |
| Interventions | Intervention Characteristics Stop (placebo) Continue | |
| Outcomes | Systolic blood pressure (sitting)
Diastolic BP (sitting)
Stroke fatal
Stroke fatal and non‐fatal
Mortality (all‐cause)
Cardiovascular mortality
Fatal and non‐fatal cardiovascular events (heart failure, hypertension, stroke)
Withdrawal due to hypertension
Withdrawal for any reason
| |
| Identification | Sponsorship source: Ontario Heart Foundation Country: Canada Setting: Two geriatric institutions Authors name: Martin G. Myers Institution: Sunnybrook Hospital Email: [email protected] Address: 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Subjects were randomly allocated to either continued diuretic therapy or placebo". Quote: "The randomization process included stratification for the presence of heart disease and/or hypertension." Judgement comment: not enough information to make judgement |
| Allocation concealment (selection bias) | Low risk | Quote: "... randomization code was kept in the Department of Pharmacy." |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "Double‐blind design." "Matching placebo tablets were available for each diuretic, Slow K and potassium chloride solution. The potassium chloride solution did not have the same taste as the active compound otherwise the placebo and active tablets were identical. None of the three subjects on placebo potassium chloride commented on a change in therapy during the study." Judgement comment: noted to be double blind. While possibility that participants could taste a difference, none commented so likely low risk |
| Blinding of outcome assessment (detection bias) | Unclear risk | Judgement comment: not enough information to make judgement |
| Incomplete outcome data (attrition bias) | High risk | Judgement comment: uneven dropouts with reasons for dropout uneven. Overall large number of dropouts/incomplete data for main outcome of BP |
| Selective reporting (reporting bias) | Unclear risk | Judgement comment: there was no protocol available, not enough information to make judgement |
| Other bias | Low risk | Judgement comment: no other areas of concern |
| Study characteristics | ||
| Methods | Study design: Randomised controlled trial Study grouping: Parallel group | |
| Participants | Number of participants randomised (discontinuation/continuation): 102/100 Baseline characteristics Stop
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Included criteria: patients aged 65 or more who had been receiving diuretics for at least six months and had no overt heart failure or hypertension Excluded criteria: history of acute heart failure, defined as admission to hospital or prescription of intravenous diuretic therapy; symptoms of heart failure during the previous three months; manifest heart failure, defined as a heart failure score of over 4; use of frusemide at dosages over 80 mg/day; mean of three blood pressure values (two measured at successive home visits and one obtained from the medical file) > 180/100 mm Hg; hypercalciuria, nephrotic syndrome, and glaucoma; use of fixed combinations of diuretics with‚blockers or angiotensin converting enzyme inhibitors; combination therapy of beta‐blockers, diuretics, and vasodilators for hypertension; use of a diuretic for which no placebo was available; and non‐compliance during the run in phase. In addition, 57 patients or their general practitioners refused to cooperate and seven eligible patients could not be enrolled in the trial for logistic reasons. Pretreatment: The two groups were similar in all relevant baseline characteristics, including age, gender, current indication for diuretic therapy, heart failure score, New York Heart Association classification, SBP, DBP. Withdrawal criteria: Patients with frusemide dosages of 40 or 80 mg/day went through a dose‐halving regimen of one and two weeks, respectively, to prevent severe rebound effects. Dose halving was started immediately after randomisation and was performed double‐blind. Process of drug withdrawal (tapering): Participants with frusemide dosages of 40 or 80 mg/day went through a dose‐halving regimen of one and two weeks, respectively, to prevent severe rebound effects. Dose halving was started immediately after randomisation and was performed double‐blind. Antihypertensives taken: frusemide (including combinations with other diuretics), thiazide (including combinations with other diuretics), triamterene monotherapy | |
| Interventions | Intervention Characteristics Stop Continue | |
| Outcomes | Systolic blood pressure
Diastolic blood pressure
Withdrawal for any reason
Withdrawal due to heart failure
Withdrawal due to hypertension
| |
| Identification | Sponsorship source: Dutch Organisation for Scientific Research (NWO, Research Grant number 920≠01≠173) Country: Netherlands Setting: Participants from eight general practices Authors name: Edmond P Walma Institution: Erasmus University Medical School, Rotterdam Email: [email protected] Address: Department of General Practice, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, Netherlands | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "... each patient was randomly assigned to placebo (the withdrawal group) or continuation of diuretic therapy (the control group), after stratification by age (65‐79 and > 80 years) and type of diuretic. Blocks of four sets of study medication each consisted of two placebo and two genuine packages, which were consecutively assigned to enrolled patients." |
| Allocation concealment (selection bias) | Low risk | Quote: "Randomisation lists and numbered sets of study medication were generated by the trial pharmacist of the Academic Hospital, who also produced sealed envelopes with decoding information for emergencies." |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "The similarity of genuine and placebo tablets ensured the possibility of recognising them by colour, form, or taste. The randomisation list remained in the pharmacy of the Academic Hospital in Rotterdam, separate from the trial centre in Schoonhoven. Of the sealed envelopes one copy was kept in the trial centre and another with the patient at home (for emergencies)." |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "The codes were broken either after the assessment of the last set of data, or when a diuretic prescription was needed, in which case the primary outcome of the study became actual." |
| Incomplete outcome data (attrition bias) | Low risk | Judgement comment: outcome recorded on all patients in the study |
| Selective reporting (reporting bias) | Low risk | Quote: "The primary outcome variable was successful withdrawal from diuretic therapy. Patients in the withdrawal group who were still taking blinded study medication at the end of the six month follow‐up period were considered successfully withdrawn. Those patients who met one of the predefined criteria for requiring diuretic therapy within the follow‐up period were considered to be unsuccessfully withdrawn. Criteria for prescription of diuretic therapy were: (a) heart failure score exceeding 4 points or (b) a mean of three duplicate systolic or diastolic blood pressure measurements on separate occasions of > 180 mm Hg or > 100 mm Hg, respectively. Further, patients in whom diuretic therapy was restarted by their doctor for other reasons — for example, symptoms of increased shortness of breath — were considered to be unsuccessfully withdrawn. Changes in systolic and diastolic blood pressures are presented as secondary outcomes." |
| Other bias | Low risk | Judgement comment: no other areas of concern |
BP: Blood pressure
CHF: Congestive heart failure
DISH: Dietary intervention study of hypertension
DBP: Diastolic blood pressure
ECG: Electrocardiogram
HDFP: Hypertension detection and follow‐up program
HTN: Hypertension
IQR: Interquartile range
ITT: Intention to treat
MI: Myocardial infarction
MMSE: Mini‐Mental State Examination
NPI: Neuropsychiatric Inventory
QOL: Quality of life
SBP: Systolic blood pressure
SE: Standard error
TIA: Transient ischaemic attack
Characteristics of excluded studies [ordered by study ID]
Ir a:
| Study | Reason for exclusion |
| One or both groups had confounding treatment (such as additional dietary or exercise intervention or other antihypertensives). | |
| Wrong patient population | |
| Wrong patient population | |
| One or both groups had confounding treatment (such as additional dietary or exercise intervention or other antihypertensives). | |
| Wrong intervention | |
| Wrong intervention | |
| Protocol paper (of an ineligible study due to wrong intervention) | |
| Wrong study design | |
| Wrong intervention | |
| Wrong intervention | |
| One or both groups had confounding treatment (such as additional dietary or exercise intervention or other antihypertensives). | |
| Wrong study design | |
| Wrong intervention | |
| One or both groups had confounding treatment (such as additional dietary or exercise intervention or other antihypertensives). | |
| One or both groups had confounding treatment (such as additional dietary or exercise intervention or other antihypertensives). | |
| Wrong patient population | |
| Wrong patient population | |
| Wrong patient population | |
| Wrong intervention | |
| Wrong patient population | |
| Wrong patient population | |
| Clinical trial registry citation (of an ineligible study due to wrong patient population) | |
| Wrong study design | |
| Wrong intervention | |
| Wrong intervention | |
| Wrong intervention | |
| One or both groups had confounding treatment (such as additional dietary or exercise intervention or other antihypertensives). | |
| Wrong intervention | |
| Wrong population as not older adults; half of participants < 50 years | |
| Wrong study design | |
| Wrong intervention | |
| Wrong patient population | |
| Wrong intervention |
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 All‐cause mortality Show forest plot | 4 | 630 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.08 [0.79, 5.46] |
| Analysis 1.1  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 1: All‐cause mortality | ||||
| 1.2 Cardiovascular mortality Show forest plot | 1 | 77 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.04 [0.21, 20.19] |
| Analysis 1.2  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 2: Cardiovascular mortality | ||||
| 1.3 Myocardial infarction (fatal and nonfatal) Show forest plot | 2 | 447 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.86 [0.19, 17.98] |
| Analysis 1.3  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 3: Myocardial infarction (fatal and nonfatal) | ||||
| 1.4 Systolic blood pressure Show forest plot | 5 | 767 | Mean Difference (IV, Fixed, 95% CI) | 9.75 [7.33, 12.18] |
| Analysis 1.4  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 4: Systolic blood pressure | ||||
| 1.5 Diastolic blood pressure Show forest plot | 5 | 768 | Mean Difference (IV, Fixed, 95% CI) | 3.50 [1.82, 5.18] |
| Analysis 1.5  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 5: Diastolic blood pressure | ||||
| 1.6 Hospitalisation Show forest plot | 1 | 385 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.83 [0.33, 2.10] |
| Analysis 1.6  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 6: Hospitalisation | ||||
| 1.7 Stroke (fatal + nonfatal + TIA) Show forest plot | 3 | 524 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.44 [0.25, 8.35] |
| Analysis 1.7  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 7: Stroke (fatal + nonfatal + TIA) | ||||
| 1.8 Sucess rate ‐ withdrawal/resumption due to hypertension or other clinical reason Show forest plot | 3 | 341 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 3.23 [1.86, 5.61] |
| Analysis 1.8  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 8: Sucess rate ‐ withdrawal/resumption due to hypertension or other clinical reason | ||||
| 1.9 Quality of life Show forest plot | 1 | 356 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐0.35, 0.15] |
| Analysis 1.9  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 9: Quality of life | ||||
| 1.10 Systolic blood pressure subgrouped on duration Show forest plot | 5 | 767 | Mean Difference (IV, Fixed, 95% CI) | 9.75 [7.33, 12.18] |
| Analysis 1.10  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 10: Systolic blood pressure subgrouped on duration | ||||
| 1.10.1 Less than 12 months | 3 | 647 | Mean Difference (IV, Fixed, 95% CI) | 9.17 [6.62, 11.71] |
| 1.10.2 12 months or longer | 2 | 120 | Mean Difference (IV, Fixed, 95% CI) | 15.30 [7.48, 23.12] |
| 1.11 Systolic blood pressure subgrouped on drug type Show forest plot | 5 | 767 | Mean Difference (IV, Fixed, 95% CI) | 9.75 [7.33, 12.18] |
| Analysis 1.11  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 11: Systolic blood pressure subgrouped on drug type | ||||
| 1.11.1 Diuretics | 4 | 411 | Mean Difference (IV, Fixed, 95% CI) | 10.85 [7.92, 13.78] |
| 1.11.2 Other | 1 | 356 | Mean Difference (IV, Fixed, 95% CI) | 7.40 [3.10, 11.70] |
| 1.12 Diastolic blood pressure subgrouped on duration Show forest plot | 5 | 768 | Mean Difference (IV, Fixed, 95% CI) | 3.50 [1.82, 5.18] |
| Analysis 1.12  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 12: Diastolic blood pressure subgrouped on duration | ||||
| 1.12.1 Less than 12 months | 3 | 646 | Mean Difference (IV, Fixed, 95% CI) | 2.68 [0.87, 4.49] |
| 1.12.2 12 months or longer | 2 | 122 | Mean Difference (IV, Fixed, 95% CI) | 8.70 [4.15, 13.25] |
| 1.13 Diastolic blood pressure subgrouped on drug type Show forest plot | 5 | 768 | Mean Difference (IV, Fixed, 95% CI) | 3.50 [1.82, 5.18] |
| Analysis 1.13  Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 13: Diastolic blood pressure subgrouped on drug type | ||||
| 1.13.1 Diuretics | 4 | 412 | Mean Difference (IV, Fixed, 95% CI) | 4.42 [2.03, 6.81] |
| 1.13.2 Other | 1 | 356 | Mean Difference (IV, Fixed, 95% CI) | 2.60 [0.24, 4.96] |
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of comparison: 1 Continuation vs discontinuation by no treatment/placebo of antihypertensives, outcome: 1.1 All‐cause mortality.
Forest plot of comparison: 1 Discontinuation by no treatment/placebo of antihypertensives vs Continuation, outcome: 1.4 Systolic blood pressure.
Forest plot of comparison: 1 Discontinuation by no treatment/placebo of antihypertensives vs Continuation, outcome: 1.12 Diastolic blood pressure sub grouped on duration of study.
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 1: All‐cause mortality
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 2: Cardiovascular mortality
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 3: Myocardial infarction (fatal and nonfatal)
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 4: Systolic blood pressure
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 5: Diastolic blood pressure
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 6: Hospitalisation
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 7: Stroke (fatal + nonfatal + TIA)
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 8: Sucess rate ‐ withdrawal/resumption due to hypertension or other clinical reason
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 9: Quality of life
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 10: Systolic blood pressure subgrouped on duration
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 11: Systolic blood pressure subgrouped on drug type
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 12: Diastolic blood pressure subgrouped on duration
Comparison 1: Discontinuation by no treatment/placebo of antihypertensives vs Continuation, Outcome 13: Diastolic blood pressure subgrouped on drug type
| Discontinuation by no treatment/placebo of antihypertensives compared to continuation in older people | ||||||
| Patient or population: Older adults, 50 years and older | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with Continuation | Risk with Discontinuation by no treatment/placebo of antihypertensives | |||||
| All‐cause mortality | Study population | OR 2.08 | 630 | ⊕⊕⊝⊝ | ||
| 19 per 1,000 | 40 per 1,000 | |||||
| Moderate | ||||||
| 26 per 1,000 | 52 per 1,000 | |||||
| Myocardial infarction (fatal and nonfatal) | Study population | OR 1.86 | 447 | ⊕⊝⊝⊝ | ||
| 5 per 1,000 | 9 per 1,000 | |||||
| Moderate | ||||||
| 3 per 1,000 | 5 per 1,000 | |||||
| Hospitalisation | Study population | OR 0.83 | 385 | ⊕⊕⊝⊝ | ||
| 54 per 1,000 | 45 per 1,000 | |||||
| Stroke (fatal + nonfatal + TIA) | Study population | OR 1.44 | 524 | ⊕⊕⊝⊝ | ||
| 8 per 1,000 | 11 per 1,000 | |||||
| Moderate | ||||||
| 5 per 1,000 | 8 per 1,000 | |||||
| Systolic blood pressure | The mean systolic blood pressure ranged from 123 to 145 mmHg 9 | MD 9.75 mmHg higher | ‐ | 767 | ⊕⊕⊝⊝ | |
| Diastolic blood pressure: range 12 weeks to 12 months | The mean diastolic blood pressure ranged from 70‐95 mmHg 9 | MD 3.5 mmHg higher | ‐ | 768 | ⊕⊕⊝⊝ | |
| Adverse drug reactions and adverse drug withdrawal reactions (adverse reactions) | Overall there was some reversal of adverse drug reactions in the discontinuation group, otherwise no change reported. One study reported no difference in frequency of side effects although data were not shown. One study reported reversal of slight postural drop and improvement in renal function and serum cholesterol in the discontinuation but not the continuation group. One study reported that more participants experienced ankle oedema in the discontinuation than the continuation group, however, statistical significance was not reported. All three studies reported changes in potassium in the discontinuation group. | ‐ | 245 | ⊕⊝⊝⊝ | ||
| Falls ‐ not reported | None of the included studies reported on falls or falls risk. | ‐ | ‐ | ‐ | ||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Not downgraded for risk of bias: some concern about attrition bias in 2 of the studies (high and uneven drop out rates), not enough to assess as serious but considered when downgrading in other areas. 2 Not downgraded for inconsistency but considered when downgrading other areas: some concern about heterogeneity due to the difference in mortality rates between Myers 1982 and Maland 1983 but likely explained by differences in populations (Maland's participants were older and recruited from geriatric institutions). 3 Downgraded one level for imprecision, the total number of events was very low ; additionally, the CI included the null effect and appreciable benefit favouring continuation. 4 Downgraded one level for indirectness due to concern about the age of the majority of studies relevant for this outcome ‐ standards of care and recommendations for treatment have significantly changed over the past 35 years. Downgrading in this category also took into account the large concern about imprecision (which was downgraded 1, but had considered downgrading 2 steps) as well as potential risk of bias and inconsistency. 5 Downgraded one level for risk of bias as neither study had blinding of participants or physicians; possible that diagnosis of MI could have been influenced by knowledge of intervention. 6 Downgraded two levels for imprecision as the total number of events was very low; additionally, the CI included the null effect and appreciable benefit favouring continuation. 7 Downgraded two levels for imprecision as the total number of events was very low; additionally, the CI included the null effect and appreciable benefit favouring discontinuation. 8 Downgraded one level for indrectness due to concern about the age of the majority of studies relevant for this outcome ‐ standards of care and recommendations for treatment have significantly changed over the past 35 years. Downgrading in this category also took into account the large concern about imprecision (which was downgraded 1, but had considered downgrading 2 steps).. 9 Range of BP at end of follow‐up period in continuation group of included studies. 10 Downgraded one level for risk of bias due to concern about lack of blinding of participants and physicians in two of the studies, uneven dropouts in two of the studies and reporting bias in one of the studies. 11 Downgraded one level for inconsistency due to substantial heterogeneity, subgroup analyses based on duration of follow‐up and class of medication was not able to explain heterogeneity, and no other cause identified. 12 Some concern about indirectness as BP is a surrogate marker, also the majority of studies are more than 35 years old. Did not downgrade in this category, however contributed to the decision to downgrade in the 'Risk of bias' category. 13 Downgraded one level for inconsistency; duration of follow‐up was able to explain some of the inconsistency, however, heterogeneity remained in the subgroup with a duration of follow‐up 12 months or greater. 14 Downgraded two levels for risk of bias due to very serious concern about lack of blinding, attrition bias and poor detection and reporting of outcome. 15 Downgraded one level for imprecision due to small sample size and number of events. TIA: Transient ischaemic attack | ||||||
| Study, country | Setting | Study duration | Antihypertensive medication class withdrawn | Discontinuation plan |
| Burr 1977, Wales | Long‐stay geriatric wards | 12 months | Diuretic | Not specified |
| Langford 1984, USA | Primary care | 56 weeks | Any antihypertensive medication | Participants were withdrawn from therapy using a standardised step‐down withdrawal programme taking from 2 to 8 weeks, depending on the number and dosage of drugs at entry. The diuretic was the last agent withdrawn. Drug withdrawal took place in a stepped fashion with the highest step drug being removed first. Target time for withdrawal was 6 weeks. |
| Maland 1983, USA | Community | 12 months | Diuretic | Not specified |
| Moonen 2015, Netherlands | 128 general practices | 16 weeks | β‐Blocker, diuretic, angiotensin‐converting enzyme inhibitor, angiotensin receptor blocker or calcium channel blocker. | The discontinuation of antihypertensive treatment was performed by the participant’s physician according to an algorithm composed by the investigators. All physicians were instructed to withdraw antihypertensive treatment until a maximum increase of 20 mmHg in SBP was reached. The physician monitored BP every week until no further changes in antihypertensive treatment were made |
| Myers 1982, Canada | Geriatric institution | 12 months | Diuretic | Not specified |
| Walma 1997, Netherlands | 8 general practices | 6 months | Diuretic | Participants with frusemide dosages of 40 or 80 mg/day went through a dose‐halving regimen of one and two weeks, respectively, to prevent severe rebound effects. Dose halving was started immediately after randomisation and was performed double‐blind. |
| BP: Blood pressure | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 All‐cause mortality Show forest plot | 4 | 630 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.08 [0.79, 5.46] |
| 1.2 Cardiovascular mortality Show forest plot | 1 | 77 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.04 [0.21, 20.19] |
| 1.3 Myocardial infarction (fatal and nonfatal) Show forest plot | 2 | 447 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.86 [0.19, 17.98] |
| 1.4 Systolic blood pressure Show forest plot | 5 | 767 | Mean Difference (IV, Fixed, 95% CI) | 9.75 [7.33, 12.18] |
| 1.5 Diastolic blood pressure Show forest plot | 5 | 768 | Mean Difference (IV, Fixed, 95% CI) | 3.50 [1.82, 5.18] |
| 1.6 Hospitalisation Show forest plot | 1 | 385 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.83 [0.33, 2.10] |
| 1.7 Stroke (fatal + nonfatal + TIA) Show forest plot | 3 | 524 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.44 [0.25, 8.35] |
| 1.8 Sucess rate ‐ withdrawal/resumption due to hypertension or other clinical reason Show forest plot | 3 | 341 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 3.23 [1.86, 5.61] |
| 1.9 Quality of life Show forest plot | 1 | 356 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐0.35, 0.15] |
| 1.10 Systolic blood pressure subgrouped on duration Show forest plot | 5 | 767 | Mean Difference (IV, Fixed, 95% CI) | 9.75 [7.33, 12.18] |
| 1.10.1 Less than 12 months | 3 | 647 | Mean Difference (IV, Fixed, 95% CI) | 9.17 [6.62, 11.71] |
| 1.10.2 12 months or longer | 2 | 120 | Mean Difference (IV, Fixed, 95% CI) | 15.30 [7.48, 23.12] |
| 1.11 Systolic blood pressure subgrouped on drug type Show forest plot | 5 | 767 | Mean Difference (IV, Fixed, 95% CI) | 9.75 [7.33, 12.18] |
| 1.11.1 Diuretics | 4 | 411 | Mean Difference (IV, Fixed, 95% CI) | 10.85 [7.92, 13.78] |
| 1.11.2 Other | 1 | 356 | Mean Difference (IV, Fixed, 95% CI) | 7.40 [3.10, 11.70] |
| 1.12 Diastolic blood pressure subgrouped on duration Show forest plot | 5 | 768 | Mean Difference (IV, Fixed, 95% CI) | 3.50 [1.82, 5.18] |
| 1.12.1 Less than 12 months | 3 | 646 | Mean Difference (IV, Fixed, 95% CI) | 2.68 [0.87, 4.49] |
| 1.12.2 12 months or longer | 2 | 122 | Mean Difference (IV, Fixed, 95% CI) | 8.70 [4.15, 13.25] |
| 1.13 Diastolic blood pressure subgrouped on drug type Show forest plot | 5 | 768 | Mean Difference (IV, Fixed, 95% CI) | 3.50 [1.82, 5.18] |
| 1.13.1 Diuretics | 4 | 412 | Mean Difference (IV, Fixed, 95% CI) | 4.42 [2.03, 6.81] |
| 1.13.2 Other | 1 | 356 | Mean Difference (IV, Fixed, 95% CI) | 2.60 [0.24, 4.96] |
