Drug Designed To Lower Uric Acid Levels May Be Useful For Hypertension

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Main Category: Hypertension
Also Included In: Blood / Hematology;  Urology / Nephrology
Article Date: 27 Aug 2008 - 3:00 PDT

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According to a report published in the August 27 issue of JAMA, a drug that lowers uric acid levels, allopurinol, also seems to lower blood pressure in adolescents with newly diagnosed hypertension (high blood pressure).

Hyperuricemia - a condition characterized by higher than normal blood levels of uric acid (a chemical found in urine and blood that results from normal bodily processes) - is commonly associated with hypertension. There has been some research to support uric acid's causal role in hypertension, but hyperuricemia is not considered a true risk factor for hypertension as high uric acid in hypertension could be due to several other factors. Experimental studies in laboratory animals, however, have challenged this belief by indicating support for a causal role of uric acid in hypertension.

To determine the effect on hypertension of a uric acid-reducing drug, Daniel I. Feig, M.D., Ph.D. (Baylor College of Medicine, Houston) and colleagues conducted a randomized, placebo-controlled "crossover" trial. The researchers studied hyperuricemic adolescents (11 to 17 years old) with newly diagnosed hypertension to see if the drug allopurinol would reduce blood pressure (BP). Feig and colleagues randomly assigned thirty participants to receive either allopurinol or placebo twice daily for four weeks. Following the initial administration, there was a two week "washout" period during which the patients did not receive anything, and then for four more weeks they received the therapy that they had not yet received.

The investigators found that allopurinol treatment was linked to a significant decrease in casual and ambulatory systolic and diastolic blood pressure. During allopurinol treatment, the average decrease in casual BP was -6.9 mm Hg systolic and -5.1 mm Hg diastolic. Participants taking placebo only presented changes of -2.0 and -2.4, respectively. The researchers also found that average changes in 24-hour ambulatory BP during allopurinol were -6.3 mm Hg, systolic and -4.6, diastolic. There were slight increases in systolic BP during the placebo phase (0.8 mm Hg) and slight decreases in diastolic BP (0.3 mm Hg). In addition, the decrease in ambulatory BP was directly correlated with allopurinol treatment. Remarkably, during the allopurinol phase 20 of the 30 patients reached normal BP by casual and ambulatory criteria compared to only 1 of 30 during the placebo phase.

"The results of this study represent a potentially new therapeutic approach, that of control of a biochemical cause of hypertension, rather than nonspecifically lowering elevated BP. Although not representing a fully developed therapeutic strategy, this study raises an alternative strategy that may prove to be more effective than currently available options," write Feig and colleagues.

They conclude: "Despite these findings, this clinical trial is a small one and allopurinol is not indicated for the treatment of hypertension in adolescents or other populations. The potential adverse effects of allopurinol, including gastrointestinal complaints and especially Stevens-Johnson syndrome [a severe, allergic reaction], make allopurinol an unattractive alternative to available antihypertensive medications. More clinical trials are needed to determine the reproducibility of the data and whether it can be generalized to the larger hypertensive population. Nevertheless, the observation that lowering uric acid can reduce BP in adolescents with newly diagnosed hypertension raises intriguing questions about its role in the pathogenesis of hypertension."

Effect of Allopurinol on Blood Pressure of Adolescents With Newly Diagnosed Essential Hypertension: A Randomized Trial
Daniel I. Feig; Beth Soletsky; Richard J. Johnson
JAMA (2008). 300[8]: pp. 924-932.
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Written by: Peter M Crosta
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