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

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Context
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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.
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<p><b>Objective </b>To determine whether lowering uric acid lowers blood pressure (BP) in hyperuricemic adolescents with newly diagnosed hypertension. </p>
<p><b>Design, Setting, and Patients </b>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 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. </p>
<p><b>Intervention </b>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. </p>
<p><b>Main Outcome Measures </b>Change in casual and ambulatory blood pressure. </p>
<p><b>Results </b>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 &lt; .001). </p>
<p><b>Conclusions </b>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.  <br /><br /><strong>Source: JAMA. 2008;300(8):924-932</strong></p>