Pharmacotherapy for hyperuricemia in hypertensive patients

Abstract

Background: High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a link between hyperuricemia and hypertension. Hyperuricemia affects 25% to 40 % of individuals with untreated hypertension; a much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (UA) might lower blood pressure (BP) is an unanswered question.

Objectives: To determine whether UA-lowering agents reduce BP in patients with primary hypertension or prehypertension compared with placebo.

Search methods: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS up to March 2016 and contacted authors of relevant papers regarding further published and unpublished work.

Selection criteria: To be included in this review, the studies had to meet the following criteria: 1) randomized or quasi-randomized, with a group assigned to receive a UA-lowering agent and another group assigned to receive placebo; 2) double-blind, single-blind or open-label; 3) parallel or cross-over trial; 4) cross-over trials had to have a washout period of at least two weeks; 5) minimum treatment duration of four weeks; 6) participants had to have a diagnosis of essential hypertension or prehypertension, and hyperuricemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men and 5.5 mg/dL in children/adolescents); 7) outcome measures assessed included change in clinic systolic, diastolic or 24-hour ambulatory BP.

Data collection and analysis: The two review authors independently collected the data using a data extraction form, and resolved any disagreements via discussion. We assessed risk of bias using the Cochrane Collaboration' Risk of bias' tool.

Main results: In this review update, we examined the abstracts of 349 identified papers and selected 21 for evaluation. We also identified three ongoing studies, the results of which are not yet available. Three other randomized controlled trials (RCTs) (two new), enrolling individuals with hypertension or prehypertension, and hyperuricemia, met the inclusion criteria for the review and were included in the meta-analysis. Low quality of evidence from three RCTs indicate no reduction in systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic (-3.9 mmHg, 95% CI -9.2 to 1.4) 24-hour ambulatory BP with UA-lowering drugs compared with placebo. Low quality of evidence from two RCTs reveal a reduction of systolic clinic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but not diastolic clinic BP (-6.45 mmHg, 95% CI -13.60 to 0.70). High quality of evidence from three RCTs indicates that serum UA levels were reduced by 3.1 mg/dL (95% CI 2.4 to 3.8) in the participants that received UA-lowering drugs. Very low quality of evidence from three RCTs suggests that withdrawals due to adverse effects were not increased with UA-lowering therapy (RR 1.86, 95% CI 0.43 to 8.10).

Authors' conclusions: In this updated systematic review, the RCT data available at present are insufficient to know whether UA-lowering therapy also lowers BP. More studies are needed.

Figure 1

Flow diagram of the study selection

Figure 2

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

Figure 3

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

Figure 4

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

Figure 5

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

Figure 6

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

Figure 7

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

Figure 8

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

Figure 9

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

Analysis 1.1

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

Analysis 1.2

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

Analysis 1.3

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

Analysis 1.4

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

Analysis 1.5

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

Analysis 1.6

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