Allopurinol is a potent xanthine oxidase inhibitor that is used in hyperuricemic patients to prevent gout. It has also been shown to decrease cardiovascular complications in a myriad of cardiovascular conditions. However, studies have reported conflicting evidence on its effects on blood pressure (BP). A systematic review was conducted using Medline, PubMed, Embase, and the Cochrane Library for all the longitudinal studies that assessed the efficacy of allopurinol on systolic and diastolic BP. A total of 10 clinical studies with 738 participants were included in the analysis. Compared with the control group, systolic BP decreased by 3.3 mm Hg (95% confidence interval [CI], 1.4-5.3 mm Hg; P=.001) and diastolic BP decreased by 1.3 mm Hg (95% CI, 0.1-2.5 mm Hg; P=.03) in patients treated with allopurinol. When analysis was restricted to the higher-quality randomized controlled trials, similar changes in systolic and diastolic BPs were found: 3.3 mm Hg (95% CI, 0.8-5.8 mm Hg; P<.001) and 1.4 mm Hg (95% CI, 0.1-2.7 mm Hg; P=.04), respectively. Allopurinol is associated with a small but significant reduction in BP. This effect can be potentially exploited to aid in controlling BP in hypertensive patients with hyperuricemia. J Clin Hypertens (Greenwich). 2013;15:435-442. Ó2012 Wiley Periodicals, Inc.Uric acid (UA) is the end product of purine metabolism catalyzed by the enzyme xanthine oxidoreductase, which is frequently elevated in patients with gout. Hyperuricemia is commonly associated with hypertension 1,2 and is present in 25% of untreated patients with hypertension, in 50% of patients taking diuretics, and in >75% of patients with malignant hypertension.
1Hypertensive patients with hyperuricemia have a 3-to 5-fold increased risk of coronary or cerebrovascular disease compared with hypertensive patients with normal UA levels.3 Allopurinol is a potential inhibitor of the xanthine oxidoreductase enzyme, a key component in the production of UA pathway. Multiple studies examining the effects of allopurinol treatment on UA levels have documented conflicting results on its effects on blood pressure (BP). [4][5][6][7] The quandary regarding the use of allopurinol was pointed out in an editorial by Michael Alderman 8 in which he noted that while the present evidence does not justify the use of hypouricemic therapy for cardioprotection, there is also no evidence to show that lowering UA levels may be harmful. However, Feig and colleagues 9 found that allopurinol significantly lowered BP in adolescents with newly diagnosed hypertension. In view of these findings, we decided to conduct a systematic review of the existing literature to examine the effect of allopurinol on BP.
MATERIALS AND METHODS
Search StrategyWe systematically searched the electronic databases, Medline, PubMed, EMBASE, and the Cochrane Library for Central Register of Clinical Trials, using the MESH terms ''allopurinol,'' ''blood pressure,'' ''blood pressure monitoring, ambulatory,'' and ''hypertension,'' with the key words ''xanthine oxidase inhibitor,'' '...
