Effect of Allopurinol on Blood Pressure of Adolescents With Newly Diagnosed Essential Hypertension

TLDR

Hyperuricemia predicts hypertension and is common in newly diagnosed essential hypertension, and animal studies show that raising uric acid with a uricase inhibitor induces systemic hypertension. The study aimed to determine whether lowering uric acid with allopurinol reduces blood pressure in hyperuricemic adolescents with newly diagnosed hypertension. In a randomized, double‑blind, placebo‑controlled crossover trial, 30 adolescents aged 11‑17 with stage 1 essential hypertension and serum uric acid ≥6 mg/dL received 200 mg allopurinol twice daily for 4 weeks and placebo for 4 weeks, with a 2‑week washout and randomized treatment order, and casual and ambulatory BP were measured. Allopurinol lowered systolic BP by an average of 6.9 mm Hg and diastolic BP by 5.1 mm Hg versus 2.0 mm Hg and 2.4 mm Hg with placebo, and 20 of 30 participants achieved normal BP on allopurinol compared to 1 on placebo, indicating a significant BP reduction but with potential adverse effects limiting its current therapeutic use. These preliminary findings (clinicaltrials.gov NCT00288184) require confirmation in larger trials.

Abstract

Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension. Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models.To determine whether lowering uric acid lowers blood pressure (BP) in hyperuricemic adolescents with newly diagnosed hypertension.Randomized, double-blind, placebo-controlled, crossover trial (September 2004-March 2007) involving 30 adolescents (aged 11-17 years) who had newly diagnosed, never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children's Hospital in Houston. Patients were excluded if they had stage 2 hypertension or known renal, cardiovascular, gastrointestinal tract, hepatic, or endocrine disease.Allopurinol, 200 mg twice daily for 4 weeks, and placebo, twice daily for 4 weeks, with a 2-week washout period between treatments. The order of the treatments was randomized.Change in casual and ambulatory blood pressure.For casual BP, the mean change in systolic BP for allopurinol was -6.9 mm Hg (95% confidence interval [CI], -4.5 to -9.3 mm Hg) vs -2.0 mm Hg (95% CI, 0.3 to -4.3 mm Hg; P = .009) for placebo, and the mean change in diastolic BP for allopurinol was -5.1 mm Hg (95% CI, -2.5 to -7.8 mm Hg) vs -2.4 (95% CI, 0.2 to -4.1; P = .05) for placebo. Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg (95% CI, -3.8 to -8.9 mm Hg) vs 0.8 mm Hg (95% CI, 3.4 to -2.9 mm Hg; P = .001) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg (-2.4 to -6.8 mm Hg) vs -0.3 mm Hg (95% CI, 2.3 to -2.1 mm Hg; P = .004) for placebo. Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo (P < .001).In this short-term, crossover study of adolescents with newly diagnosed hypertension, treatment with allopurinol resulted in reduction of BP. The results represent a new potential therapeutic approach, although not a fully developed therapeutic strategy due to potential adverse effects. These preliminary findings require confirmation in larger clinical trials.clinicaltrials.gov Identifier: NCT00288184.