Pharmacotherapy for hyperuricemia in hypertensive patients

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 linkage between hyperuricemia and hypertension. Hyperuricemia affects 25-40 % of patients with untreated hypertension. A much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (SUA) might lower blood pressure (BP) is an unanswered question. Objectives To determine whether uric acid lowering agents reduce BP in patients with primary hypertension. Search methods Electronic searches of the following sources were performed without language restriction: Cochrane Hypertension Group Specialised Register (1946 to May 2012), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012 Issue 4), MEDLINE (1946 to May 2012), EMBASE (1974 toMay 2012), LILACS (1982 to July 2012), Scirus and ClinicalTrials.gov. Authors of relevant papers were also contacted regarding further published and unpublished work. Selection criteria To be included in this review, the studies had to meet the following criteria: 1) Randomised or quasi-randomised with a group assigned to receive a uric acid lowering agent and another group assigned to receive placebo; 2) Double-blind, single-blind or open label; 3) Parallel or crossover trial; 4) For crossover trial, a washout period of at least two weeks; 5) Minimum treatment duration of four weeks; 6) Participants with diagnosis of essential hypertension and hyperuricemia, serum uric acid greater than 6 in women, 7 in men and 5.5 in children/adolescents; 7) Outcome measures includes change in casual or ambulatory, systolic or diastolic blood pressure. Data collection and analysis Two independent reviewers collected the data using a data extraction form. Disagreements were resolved by discussion. Risk of bias was accessed by the Cochrane Collaboration Risk of Bias Tool. Main results Three hundred and thirty-six abstracts were examined. One study (enrolling hypertensive and hyperuricemic patients) met the inclusion criteria for the review and was independently rated by both authors. No other studies were identified by the supplementary searches. The study identified as eligible for this review was a randomised controlled trial conducted in the USA (FEIG 2008). This well designed double-blind, placebo-controlled, crossover trial randomised 30 adolescents (11-17 years), newly diagnosed stage 1 primary hypertension and with SUA >= 6mg/dl, to receive allopurinol 200 mg twice daily for 4 weeks, and placebo for 4 weeks, with a 2 week washout period between treatments. Casual BP during the allopurinol phase decreased -6.9 mmHg (95 % CI, -4.5 to -9.3), systolic, and -5.1 mmHg (95 % CI, -2.5 to -7.8), diastolic, versus during the placebo phase, -2.0 mmHg (95 % CI, 0.3 to -4.3) systolic and -2.4 mmHg (95 % CI, 0.2 to -4.1) diastolic. For the secondary outcome (change in 24 ambulatory BP), change in systolic BP with allopurinol was -6.3 mmHg (95 % CI, -3.8 to -8.9), systolic, and -4.6 mmHg (95% CI, -2.4 to -6.8), diastolic, and with placebo, 0.8 mmHg (95 % CI, 3.4 to -2.9) systolic and -0.3 mmHg (95 % CI, 2.3 to -2.1) diastolic. P-value results ranged from 0.004 to 0.05. No participant dropout occurred and no adverse effects were seen in patients treated with allopurinol. Authors' conclusions Meta-analysis was not possible in this systematic review. In the one study that matched the inclusion criteria allopurinol decreased " in office" and ambulatory systolic and diastolic BP. Because there was only one included RCT, the number of patients providing data on pharmacotherapy for hyperuricemia in hypertension is small and restricted to adolescents with recently diagnosed mild essential hypertension. Hence, there is insufficient evidence to recommend the use of allopurinol or other hypouricemic drugs as an initial or adjuvant treatment of hypertension and more RCTs are needed.