Allopurinol on Hypertension: Insufficient Evidence to Recommend

Abstract

To the Editor: In the review “Effect of Allopurinol on Blood Pressure: A Systematic Review and Meta-Analysis,” the authors conclude that allopurinol and other xanthine oxidase inhibitors may be used as adjunctive antihypertensive agent. This meta-analysis was performed that included heterogeneous studies as well as trials with poor methodological quality, eg, Siu and colleagues (2006) (an open, nonplacebo-controlled trial including individuals with and without hypertension in which allopurinol decreased only systolic blood BP); Kanbay and colleagues (2007) (open, nonrandomized, nonplacebo-controlled study enrolling normotensive and hypertensive individuals); and Kanbay and colleagues (2011) (an open, nonplacebo-controlled trial including adults with normal blood pressure. Positive results of allopurinol were seen in decreasing systolic but not diastolic BP). Inclusion of these studies may have strengthened the BP-lowering effect of allopurinol. Furthermore, one can reasonably assume that several studies enrolling normotensive individuals are inadequate to support the conclusion that allopurinol may be used to treat hypertension. In the systematic review “Pharmacotherapy for Hyperuricemia in Hypertensive Patients” (Cochrane Database of Systematic Reviews), which has more rigorous entry criteria, the authors found that, to date, there is only one study designed to answer whether allopurinol treatment has a positive effect in reducing BP in hypertensive individuals. Feig and colleagues conducted a double-blind, placebo-controlled, crossover trial that randomized 30 adolescents (11–17 years), newly diagnosed with stage I primary hypertension and with serum uric acid >6 mg/dL, to receive allopurinol 200 mg twice daily for 4 weeks and placebo for 4 weeks with a 2-week washout period between treatments. Although it was a well-conducted study, it had a few limitations, as follows: small sample size; exclusion of more severe hypertensive individuals; short duration of treatment, not sufficient to detect adverse events associated with allopurinol or to evaluate whether the effect on BP is sustained after long-term therapy; and the reserved external validity, extending only to adolescents with mild new diagnosis of hypertension. Another concern is how clinicians might interpret the conclusion of this review. Treatment with allopurinol is not free of risks and interactions. Although rare, serious side effects can be associated with allopurinol therapy, such as fatal Stevens-Johnson syndrome and chronic interstitial nephritis. Therefore, increased incidence of side effects can be observed with the increased prescription of allopurinol. Thus, in light of current evidence, recommendation (or encouraging use) of allopurinol or other hypouricemic agent as initial or adjuvant treatment of hypertension is premature and more “RCTs” are needed.