Pharmacotherapy for hyperuricemia in hypertensive patients

Pedro Henrique França Gois; Edison Regio de Moraes Souza

doi:10.1002/14651858.CD008652.pub3

Farmacoterapia para la hiperuricemia en pacientes con hipertensión

Collapse all Expand all

References

References to studies included in this review

Jump to:

excluded studies
ongoing studies
additional references
other published versions

Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension. Journal of the American Medical Association 2008;300(8):924‐32.

NCT01496469. Effect of febuxostat on blood pressure [A phase 2, double‐blind, placebo‐controlled study to assess the effect of febuxostat 80 mg once daily compared to placebo on ambulatory blood pressure in subjects with hyperuricemia and hypertension]. clinicaltrials.gov/ct2/show/NCT01496469 (first received 18 December 2011).

Soletsky B, Feig DI. Uric acid reduction rectifies prehypertension in obese adolescents. Hypertension 2012;60(5):1148‐56.

References to studies excluded from this review

Jump to:

included studies
ongoing studies
additional references
other published versions

Assadi F. Allopurinol enhances the blood pressure lowering effect of enalapril in children with hyperuricemic essential hypertension. Journal of Nephrology 2014;27(1):51‐6.

Feig DI, Nakagawa T, Karumanchi SA, Oliver WJ, Kang DH, Finch J, et al. Hypothesis: uric acid, nephron number, and the pathogenesis of essential hypertension. Kidney International 2004;66(1):281‐7.

Higgins P, Walters MR, Murray HM, McArthur K, McConnachie A, Lees KR, et al. Allopurinol reduces brachial and central blood pressure, and carotid intima‐media thickness progression after ischaemic stroke and transient ischaemic attack: a randomised controlled trial. Heart 2014;100(14):1085‐92.

Hosoya T, Ohno I, Nomura S, Hisatome I, Shunya U, Fujimori S, et al. Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout. Clinical and Experimental Nephrology 2014;18(6):876‐84.

Jalalzadeh M, Nurcheshmeh Z, Mohammadi R, Mousavinasab N, Ghadiani MH. The effect of allopurinol on lowering blood pressure in hemodialysis patients with hyperuricemia. Journal of Research in Medical Sciences 2012;17(11):1039‐46.

Kanbay M, Ozkara A, Selcoki Y, Isik B, Turgut F, Bavbek N, et al. Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal function. International Urology and Nephrology 2007;39(4):1227‐33.

Kanbay M, Huddam B, Azak A, Solak Y, Kadioglu GK, Kirbas I, et al. A randomized study of allopurinol on endothelial function and estimated glomerular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clinical Journal of the American Society of Nephrology 2011;6(8):1887‐94.

Kim HA, Seo Y, Song YW. Four‐week effects of allopurinol and febuxostat treatments on blood pressure and serum creatinine level in gouty men. Journal of Korean Medical Science 2014;29(8):1077‐81.

Kostka‐Jeziorny K, Uruski P, Tykarski A. Effect of allopurinol on blood pressure and aortic compliance in hypertensive patients. Blood Pressure 2011;20(2):104‐10.

Madero M, Castellanos FER, Jalal D, Villalobos‐Martın M, Salazar J, Vazquez‐Rangel A, et al. A pilot study on the impact of a low fructose diet and allopurinol on clinic blood pressure among overweight and prehypertensive subjects: a randomized placebo controlled trial. Journal of the American Society of Hypertension 2015;9(11):837‐44.

Peixoto MRG, Monego ET, Jardim PCBV, Carvalho MM, Sousa ALL, Oliveira JS, et al. Diet and medication in the treatment of hyperuricemia in hypertensive patients. Arquivos Brasileiros de Cardiologia 2001;76(6):468‐72.

Pour‐Pouneh M, Narimani R, Mardani S, Momeni A, Nasri H. Evaluation of the relationship between the reduction of serum uric acid level and control of blood pressure in patients with hypertension and hyperuricemia. Journal of Isfahan Medical School 2015;33:1672‐85.

Google Scholar

Schackis RC. Hyperuricaemia and preeclampsia: is there a pathogenic link?. Medical hypotheses 2004;63(2):239‐44.

Segal MS, Srinivas TR, Mohandas R, Shuster JJ, Wen X, Whidden E, et al. The effect of the addition of allopurinol on blood pressure control in African Americans treated with thiazide‐like diuretic. Journal of the American Society of Hypertension 2015;9(8):610‐619.

Sezai A, Soma M, Nakata K, Hata M, Yoshitake I, Wakui S, et al. Comparison of febuxostat and allopurinol for hyperuricemia in cardiac surgery patients (NU‐FLASH Trial). Circulation Journal 2013;77(8):2043‐9.

Siu YP, Leung KT, Tong MKH, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. American Journal of Kidney Disease 2005;47(1):51‐9.

Tani S, Nagao K, Hirayama A. Effect of febuxostat, a xanthine oxidase inhibitor, on cardiovascular risk in hyperuricemic patients with hypertension: a prospective, open‐label, pilot study. Clinical Drug Investigation 2015;35(12):823‐31.

Whelton A, Macdonald P, Hunt B, Gunawardhana L. Hypertension in hyperuricemic gout subjects receiving febuxostat or allopurinol. Journal of Clinical Hypertension 2011;13(S1):A57.

Google Scholar

References to ongoing studies

Jump to:

included studies
excluded studies
additional references
other published versions

Influence of XOI, febuxostat, on vascular function in patients with hyperuricemia and cardiovascular risk factors.. Ongoing studyOctober 2015..

The effect of allopurinol on serum uric acid level and arterial blood pressure in hemodialysis patients.. Ongoing studyDecember 2014..

The effect of the combination of antihypertensive and urate‐lowering therapy on vascular endothelial function in patients with hypertensive and asymptomatic hyperuricemia.. Ongoing studyDecember 2013.

Additional references

Jump to:

included studies
excluded studies
ongoing studies
other published versions

Agarwal V, Hans N, Messerli FH. Effect of allopurinol on blood pressure: a systematic review and meta‐analysis. Journal of Clinical Hyprtension (Greenwich) 2013;15(6):435‐42.

Alper AB, Chen W, Yau L, Srinivasan SR, Berenson GS, Hamm LL. Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study. Hypertension 2005;45(1):34‐8.

Cannon PJ, Stason WB, Demartini FE, Sommers SC, Laragh JH. Hyperuricemia in primary and renal hypertension. New England Journal of Medicine 1966;275(9):457–64.

Carretero OA, Oparil S. Essential hypertension: part I: definition and etiology. Circulation 2000;101(3):329‐35.

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. Journal of the American Medical Association 2003;289(19):2560‐72.

de A Coutinho T, Turner ST, Kullo IJ. Serum uric acid is associated with microvascular function in hypertensive individuals. Journal of Human Hypertension 2007;21(8):610‐5.

Feig DI, Mazzali M, Kang DH, Nakagawa T, Price K, Kannelis J, et al. Serum uric acid: a risk factor and a target for treatment?. Journal of the American Society of Nephrology 2006;17:S69–S73.

Germino W. The management and treatment of hypertension. Clinical Cornerstone 2009;9(Suppl 3):S27‐33.

Gois PH, Luchi WM, Seguro AC. Allopurinol on hypertension: insufficient evidence to recommend. Journal of Clinical Hypertension (Greenwich) 2013;15:700.

Higgins JP, Green S. editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Hunt SC, Stephenson SH, Hopkins PN, Williams RR. Predictors of an increased risk of future hypertension in Utah. A screening analysis. Hypertension 1991;17:969‐76.

Jindal K, Chan CT, Deziel C, Hirsch D, Soroka SD, Tonelli M, et al. Hemodialysis adequacy in adults. Journal of the American Society of Nephrology 2006;17:S1‐27.

Johnson RJ, Feig DI, Herrera‐Acosta J, Kang DH. Resurrection of uric acid as a causal risk factor in essential hypertension. Hypertension 2005;45:18‐20.

Kasper DL, Braunwald E, Hauser S, et al. Harrison´s Principles of Internal Medicine. 16th Edition. McGraw‐Hill, 2004.

National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for 2006 Updates: Hemodialysis Adequacy, Peritoneal Dialysis Adequacy and Vascular Access. American Journal of Kidney Diseases 2006;48(Suppl 1):S1‐322.

PubMed

Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365(9455):217‐23.

Kinsey D, Walther R, Sise HS, Whitelaw G, Smithwick R. Incidence of hyperuricemia in 400 hypertensive subjects. Circulation 1961;24:972‐3.

Google Scholar

Mazzali M, Kanellis J, Han L, Feng L, Xia YY, Chen Q, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure‐independent mechanism. American Journal of Physiology ‐ Renal Physiology 2002;282:F991–7.

Mittal BV, Singh AK. Hypertension in the developing world: challenges and opportunities. American Journal of Kidney Diseases 2010;55(3):590‐8.

Ouppatham S, Bancha S, Choovichian P. The relationship of hyperuricemia and blood pressure in the Thai army population. Journal of Postgraduate Medicine 2008;54(4):259‐62.

National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics 2004;114:555‐76.

Perlstein TS, Gumieniak O, Williams GH, Sparrow D, Vokonas PS, Gaziano M, et al. Uric acid and the development of hypertension: the Normative Aging Study. Hypertension 2006;48:1031‐6.

Poon SH, Hall HA, Zimmermann B. Approach to the treatment of hyperuricemia. Medicine and Health, Rhode Island 2009;92(11):359‐62.

Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Sachs L, Batra KL, Zimmermann B. Medical implications of hyperuricemia. Medicine and Health, Rhode Island 2009;92(11):353‐5.

Sundström J, Sullivan L, D'Agostino RB, Levy D, Kannel WB, Vasan RS. Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 2005;45:28‐33.

Taniguchi Y, Hayashi T, Tsumura K, Endo G, Fujii S, Okada K. Serum uric acid and the risk for hypertension and type 2 diabetes in Japanese men: the Osaka Health Survey. Journal of Hypertension 2001;19(7):1209‐15.

Trachtman H. Treatment of hyperuricemia in essential hypertension. Hypertension 2007;49:e45.

Williams B. The year in hypertension. Journal of the American College of Cardiology 2010;55(1):65‐73.

References to other published versions of this review

Jump to:

included studies
excluded studies
ongoing studies
additional references

Gois PHF, Souza ERDM. Pharmacotherapy for hyperuricemia in hypertensive patients. Cochrane Database of Systematic Reviews 2013, Issue 1. [DOI: 10.1002/14651858.CD008652]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

excluded studies
ongoing studies

Feig 2008

Methods	Randomized, double‐blind, placebo‐controlled, cross‐over trial. Blinding: principal investigator ‐ yes, study staff ‐ yes. Length of intervention: 4 weeks. Washout: 2 weeks.
Participants	30 adolescents, 11‐17 years old. Dropout: none. Stage 1 essential hypertension: secondary causes ruled out, BP > 95th percentile (systolic or diastolic) ‐ 4th report of the task force on the diagnosis of hypertension in children and adolescents. Excluded: prehypertension or stage 2 hypertension. Uric acid: ≥ 6 mg/dL.
Interventions	Allopurinol 200 mg orally twice daily or placebo. Medication preparation: identical. All participants received dietary counselling for hypertension.
Outcomes	Primary outcome: clinic BP monitoring. Secondary outcome: 24‐hour ambulatory BP monitoring.
Notes	Clinic BP and 24‐hour ambulatory BP monitoring were measured three to seven days before initiation of any medication and on the last day of each of medication phases.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random numbers table.
Allocation concealment (selection bias)	Low risk	Pharmacy‐controlled randomization.
Incomplete outcome data (attrition bias) All outcomes	Low risk	None.
Selective reporting (reporting bias)	Low risk	Prespecified primary and secondary outcomes were described.
Other bias	Low risk	None.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Drugs provided in identical, unmarked capsules.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Both principal investigator and study staff were blind to medication assignment and serum uric acid levels until data collection completed. The order of treatment was randomized.

NCT01496469

Methods	Multicentric, phase 2, randomized, double‐blind, placebo‐controlled trial.
Participants	≥ 18 years old; documented hypertension; serum uric acid ≥7.0 mg/dL not associated with gout.
Interventions	Febuxostat 80 mg orally daily or placebo.
Outcomes	Change in systolic and diastolic 24‐hour ambulatory BP; change in serum uric acid.
Notes	24‐hour ambulatory BP monitoring was performed after six weeks of treatment (either with febuxostat or placebo) and compared with the baseline.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information reported.
Allocation concealment (selection bias)	Unclear risk	Insufficient information reported.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data balanced across intervention groups; similar reasons for missing data across groups.
Selective reporting (reporting bias)	Low risk	Prespecified primary and secondary outcomes were described.
Other bias	Unclear risk	Insufficient information reported.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information reported.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information reported.

Soletsky 2012

Methods	Randomized, double‐blind, placebo‐controlled, parallel study. Blinding: principal investigator ‐ yes, study staff ‐ yes. Length of intervention: 8 weeks.
Participants	58 adolescents, 11‐17 years old. Dropout: 4 (1 participant in the placebo group, 1 participant in the allopurinol group and 2 subjects in the probenecid group). Reason for dropout was explained only for the allopurinol group. Prehypertension: BP ≥ 90th percentile or odds ratio ≥ 120 x 80 mmHg ‐ 4th report of the task force on the diagnosis of hypertension in children and adolescents. Excluded: hypertension stage 1 and 2, renal dysfunction (serum creatinine above the normal range). Uric acid: ≥ 5 mg/dL; however, the lowest serum uric acid in the study population was 6.5 mg/dL.
Interventions	In the first week: allopurinol 100 mg twice daily; probenecid 250 mg twice daily. In the following 7 weeks: allopurinol 200 mg twice daily; probenecid 500 mg twice daily. Medication preparation: identical. All participants received dietary counselling for hypertension.
Outcomes	Primary outcome: clinic BP monitoring. Secondary outcome: 24‐hour ambulatory BP monitoring.
Notes	Clinic BP was measured three to seven days before initiation of medication and on the last day of study phases. 24‐hour ambulatory BP monitoring was completed before the end of treatment phase.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random numbers table.
Allocation concealment (selection bias)	Low risk	Pharmacy‐prepared medications.
Incomplete outcome data (attrition bias) All outcomes	Low risk	None.
Selective reporting (reporting bias)	Low risk	Prespecified primary and secondary outcomes were described.
Other bias	Low risk	None.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Drugs provided in identical, unmarked capsules.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Both principal investigator and study staff were blind to medication assignment and serum uric acid levels.

BP = blood pressure

Characteristics of excluded studies [ordered by study ID]

Jump to:

included studies
ongoing studies

Study	Reason for exclusion
Assadi 2014	This study has at least two important sources of bias: absence of a placebo group and BP measurement relied on auscultation in an open‐label trial.
Feig 2004	Non‐placebo controlled, pilot study.
Higgins 2014	Participants were normouricemic. Minor: only 42% of the participants had a diagnosis of hypertension.
Hosoya 2014	Major: uncertain prevalence of hypertension among study participants. Minor: study included individuals with chronic kidney disease.
Jalalzadeh 2012	Major: non‐placebo controlled. Minor: low dialysis adequacy and variable mean duration of dialysis.
Kanbay 2007	Major: non‐placebo controlled trial. Minor: control group combined individuals with and without hypertension; control group was not adequately designed (matched only age and sex).
Kanbay 2011	Population studied consisted of normotensive individuals.
Kim 2014	Post‐hoc analysis. Normotensive individuals.
Kostka‐Jeziorny 2011	Non‐placebo controlled. Not all the participants defined as hyperuricemic.
Madero 2015	Most participants presented normal serum uric acid levels.
O`Connor 2014	Non‐published study. The author did not provide the data from the study.
Peixoto 2001	Major: non‐placebo controlled trial. Minor: change on BP was evaluated but not considered an outcome.
Pour‐Pouneh 2015	Major methodological issues.
Schakis 2004	Major: BP levels not shown and marked difference between pathogenesis of essential hypertension and pre‐eclampsia; not all the participants defined as hyperuricemic. Minor: short term treatment and treatment duration not uniform among patients.
Segal 2015	Participants were normouricemic at the beginning of the treatment phase with allopurinol. Minor: controlled BP levels before commencing allopurinol.
Sezai 2013	Non‐placebo controlled. Participants were normotensive.
Siu 2006	Non‐placebo controlled. Minor: study conducted in patients with substantially impaired renal function.
Tani 2015	Non‐placebo controlled.
Whelton 2011	Retrospective analysis.

BP = blood pressure

Characteristics of ongoing studies [ordered by study ID]

Jump to:

included studies
excluded studies

Eguchi 2015

Trial name or title	Influence of XOI, febuxostat, on vascular function in patients with hyperuricemia and cardiovascular risk factors.
Methods	Interventional, parallel, randomised trial.
Participants	Included adults with hypertension and hyperuricemia.
Interventions	Febuxostat starting .at 10 mg, and then increased to 20 and 40 mg after 4 and 8 weeks, respectively. Allopurinol starting at 100 mg/day, and then increased to 200 mg after 4 weeks.
Outcomes	Changes in flow‐mediated dilatation, pulse wave velocity, central pressure, carotid intima‐media thickness at 6 months after the intervention.
Starting date	October 2015.
Contact information	Dr Kazuo Eguchi, Jichi Medical University School of Medicine Division of Cardiovascular Medicine, Department of Medicine.
Notes	Authors did not respond to our contact regarding preliminary data of the study.

Omrani 2014

Trial name or title	The effect of allopurinol on serum uric acid level and arterial blood pressure in hemodialysis patients.
Methods	Single‐blind, placebo‐controlled, parallel trial.
Participants	Patients with: hypertension; hyperuricemia; on dialysis for at least 3 months; not taking diuretics or other uric acid‐lowering agents.
Interventions	Allopurinol 100 mg/day for 3 months; multivitamins one tablet daily for 3 months.
Outcomes	Blood pressure; uric acid; and side effects.
Starting date	December 2014.
Contact information	Dr Omrani, Kermanshah Imam reza Hospital Internal office Kermanshah, Islamic Republic of Iran.
Notes	Authors did not respond to our contact regarding preliminary data of the study.

Yuan 2013

Trial name or title	The effect of the combination of antihypertensive and urate‐lowering therapy on vascular endothelial function in patients with hypertensive and asymptomatic hyperuricemia.
Methods	Randomized, parallel, controlled trial
Participants	Participants aged between 18 and 60 years old with: hypertension without treatment, or mild‐to‐moderate hypertension with antihypertensive agents; serum uric acid > 7 mg/dL; uric acid clearance (Cua) < 6.2 ml/min, Cua/Ccr ratio < 5%.
Interventions	Control group: antihypertensive and lifestyle change. Intervention group: antihypertensive, lifestyle intervention and benzbromarone
Outcomes	Primary: flow mediated dilation; pulse wave velocity; endothelial microparticles EM. Secondary: hypersensitivity C‐reactive protein; urinary microalbuminuria; atherogenic index of plasma.
Starting date	December 2013
Contact information	Dr Yuan, China‐Japan Friendship Hospital
Notes	Authors did not respond to our contact regarding preliminary data of the study.

Data and analyses

Open in table viewer

Comparison 1. Uric acid (UA) lowering drug vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 24h‐Systolic Blood Pressure Show forest plot	3	229	Mean Difference (Random, 95% CI)	‐6.19 [‐12.82, 0.45]
Open in figure viewer Analysis 1.1 Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 1 24h‐Systolic Blood Pressure.
2 24h‐Diastolic Blood Pressure Show forest plot	3	229	Mean Difference (Random, 95% CI)	‐3.92 [‐9.19, 1.36]
Open in figure viewer Analysis 1.2 Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 2 24h‐Diastolic Blood Pressure.
3 Clinic Systolic Blood Pressure Show forest plot	2	120	Mean Difference (Random, 95% CI)	‐8.43 [‐15.24, ‐1.62]
Open in figure viewer Analysis 1.3 Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 3 Clinic Systolic Blood Pressure.
4 Clinic Diastolic Blood Pressure Show forest plot	2	120	Mean Difference (Random, 95% CI)	‐6.45 [‐13.60, 0.70]
Open in figure viewer Analysis 1.4 Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 4 Clinic Diastolic Blood Pressure.
5 Serum uric acid Show forest plot	3	223	Mean Difference (Random, 95% CI)	‐3.09 [‐3.76, ‐2.43]
Open in figure viewer Analysis 1.5 Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 5 Serum uric acid.
6 Withdrawals due to adverse effects Show forest plot	3	241	Risk Ratio (M‐H, Random, 95% CI)	1.86 [0.43, 8.10]
Open in figure viewer Analysis 1.6 Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 6 Withdrawals due to adverse effects.

Figure 1

Flow diagram of the study selection

Navigate to figure in ReviewOpen in new tab

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Navigate to figure in ReviewOpen in new tab

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Navigate to figure in ReviewOpen in new tab

Figure 4

Forest plot of comparison: 1 Uric acid (UA)‐lowering drug vs. placebo, outcome: 1.1 systolic 24‐hour ambulatory blood pressure.

Navigate to figure in ReviewOpen in new tab

Figure 5

Forest plot of comparison: 1 Uric acid (UA)‐lowering drug vs. placebo, outcome: 1.2 diastolic 24‐hour ambulatory blood pressure.

Navigate to figure in ReviewOpen in new tab

Figure 6

Forest plot of comparison: 1 Uric acid (UA)‐lowering drug vs. placebo, outcome: 1.3 Clinic systolic blood pressure.

Navigate to figure in ReviewOpen in new tab

Figure 7

Forest plot of comparison: 1 Uric acid (UA)‐lowering drug vs. placebo, outcome: 1.4 clinic diastolic blood pressure.

Navigate to figure in ReviewOpen in new tab

Figure 8

Forest plot of comparison: 1 Uric acid (UA)‐lowering drug vs. placebo, outcome: 1.5 serum uric acid.

Navigate to figure in ReviewOpen in new tab

Figure 9

Forest plot of comparison: 1 Uric acid (UA)‐lowering drug vs placebo, outcome: 1.6 Withdrawals due to adverse effects.

Navigate to figure in ReviewOpen in new tab

Analysis 1.1

Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 1 24h‐Systolic Blood Pressure.

Navigate to figure in ReviewOpen in new tab

Analysis 1.2

Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 2 24h‐Diastolic Blood Pressure.

Navigate to figure in ReviewOpen in new tab

Analysis 1.3

Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 3 Clinic Systolic Blood Pressure.

Navigate to figure in ReviewOpen in new tab

Analysis 1.4

Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 4 Clinic Diastolic Blood Pressure.

Navigate to figure in ReviewOpen in new tab

Analysis 1.5

Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 5 Serum uric acid.

Navigate to figure in ReviewOpen in new tab

Analysis 1.6

Comparison 1 Uric acid (UA) lowering drug vs placebo, Outcome 6 Withdrawals due to adverse effects.

Navigate to figure in ReviewOpen in new tab

Summary of findings for the main comparison. Uric acid (UA) lowering drug compared to placebo for hyperuricemia in hypertensive patients

Uric acid (UA)‐lowering drug compared to placebo for hyperuricemia in hypertensive patients
Patient or population: hyperuricemia in hypertensive patients Setting: several sites in the USA Intervention: uric acid (UA)‐lowering drug Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Risk with placebo	Risk with Uric acid (UA) lowering drug	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
24h‐Systolic Blood Pressure	‐	MD 6.19 lower (12.82 lower to 0.45 higher)	MD ‐6.2 (‐12.8, 0.5)	229 (3 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
24h‐Diastolic Blood Pressure	‐	MD 3.92 lower (9.19 lower to 1.36 higher)	MD ‐3.9 (‐9.2, 1.4)	229 (3 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
Clinic Systolic Blood Pressure	‐	MD 8.43 lower (15.24 lower to 1.62 lower)	MD ‐8.4 (‐15.2, ‐1.6)	120 (2 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
Clinic Diastolic Blood Pressure	‐	MD 6.45 lower (13.6 lower to 0.7 higher)	MD ‐6.5 (‐13.6, 0.7)	120 (2 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}
Serum uric acid	‐	MD 3.09 lower (3.76 lower to 2.43 lower)	MD ‐3.1 (‐3.8, ‐2.4)	223 (3 RCTs)	⊕⊕⊕⊕ HIGH
Withdrawals due to adverse effects	18 per 1,000	34 per 1,000 (8 to 147)	RR 1.86 (0.43 to 8.10)	241 (3 RCTs)	⊕⊝⊝⊝ VERY LOW ^{1 3 4}	NCT01496469 reported only one withdrawal due to adverse events. However, four adverse events were described in the febuxostat group, which might be drug‐related. Therefore, we decided to include all four cases in the assessment of RR for this study.
*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). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; RCT: Randomized controlled trial.
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded for wide CIs ² Downgraded for high unexplained heterogeneity ³ Downgraded for small number of events and incomplete reporting ⁴ Unclear randomisation processes in the largest trial (highest weight in meta‐analysis)

Summary of findings for the main comparison. Uric acid (UA) lowering drug compared to placebo for hyperuricemia in hypertensive patients

Navigate to table in Review

Comparison 1. Uric acid (UA) lowering drug vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 24h‐Systolic Blood Pressure Show forest plot	3	229	Mean Difference (Random, 95% CI)	‐6.19 [‐12.82, 0.45]

2 24h‐Diastolic Blood Pressure Show forest plot	3	229	Mean Difference (Random, 95% CI)	‐3.92 [‐9.19, 1.36]

3 Clinic Systolic Blood Pressure Show forest plot	2	120	Mean Difference (Random, 95% CI)	‐8.43 [‐15.24, ‐1.62]

4 Clinic Diastolic Blood Pressure Show forest plot	2	120	Mean Difference (Random, 95% CI)	‐6.45 [‐13.60, 0.70]

5 Serum uric acid Show forest plot	3	223	Mean Difference (Random, 95% CI)	‐3.09 [‐3.76, ‐2.43]

6 Withdrawals due to adverse effects Show forest plot	3	241	Risk Ratio (M‐H, Random, 95% CI)	1.86 [0.43, 8.10]

Comparison 1. Uric acid (UA) lowering drug vs placebo

Navigate to table in Review

	Cochrane Review language Select your preferred language for Cochrane Reviews and other content. Sections without translation will be in English.

	Website language Select your preferred language for the Cochrane Library website.

Cochrane Review language

Website language

References

References to studies included in this review

Feig 2008 {published data only}

NCT01496469 {unpublished data only}

Soletsky 2012 {published data only}

References to studies excluded from this review

Assadi 2014 {published data only}

Feig 2004 {published data only}

Higgins 2014 {published data only}

Hosoya 2014 {published data only}

Jalalzadeh 2012 {published data only}

Kanbay 2007 {published data only}

Kanbay 2011 {published data only}

Kim 2014 {published data only}

Kostka‐Jeziorny 2011 {published data only}

Madero 2015 {published and unpublished data}

O`Connor 2014 {unpublished data only}

Peixoto 2001 {published data only}

Pour‐Pouneh 2015 {published data only}

Schakis 2004 {published data only}

Segal 2015 {published data only}

Sezai 2013 {published data only}

Siu 2006 {published data only}

Tani 2015 {published data only}

Whelton 2011 {published data only}

References to ongoing studies

Eguchi 2015 {unpublished data only}

Omrani 2014 {unpublished data only}

Yuan 2013 {unpublished data only}

Additional references

Agarwal 2013

Alper 2005

Cannon 1966

Carretero 2000

Chobanian 2003

de A Coutinho 2007

Feig 2006

Germino 2009

Gois 2013

Higgins 2011

Hunt 1991

Jindal 2006

Johnson 2005

Kasper 2004

KDOQI 2006

Kearney 2005

Kinsey 1961

Mazzali 2002

Mittal 2010

Ouppatham 2008

PEDIATRICS 2004

Perlstein 2006

Poon 2009

RevMan 5.3 [Computer program]

Sachs 2009

Sundström 2005

Taniguchi 2001

Trachtman 2007

Williams 2010

References to other published versions of this review

Gois 2013a

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Characteristics of ongoing studies [ordered by study ID]

Data and analyses

Copy or download citation

Cochrane Review language

Website language

Previously accessed institutions

Institutional users

Previously accessed institutions

Other access options