Old gout drug learns new cardiac tricks



SAN FRANCISCO – The venerable antihyperuricemic agent allopurinol has shown early promise for two novel cardiovascular applications: prevention of atrial fibrillation in the setting of heart failure and reduction of left ventricular hypertrophy in patients with type 2 diabetes.

Allopurinol is a xanthine oxidase inhibitor and antigout drug. The rationale for the drug’s use in reducing the incidence of atrial fibrillation in patients with heart failure lies in the observation that serum uric acid has emerged as an independent marker of mortality and a predictor of new-onset atrial fibrillation in heart failure. Xanthine oxidase is not only a source of reactive oxygen species that adversely affect myocardial function, but it also catalyzes the conversion of xanthine to uric acid, Dr. Fernando E. Hernandez explained at the annual meeting of the American College of Cardiology.

He presented a retrospective cohort study involving 603 patients enrolled in the Miami Veterans Affairs heart failure clinic. The 103 on allopurinol, and the 500 who were not, matched up well in terms of baseline characteristics including age, prevalence of coronary artery disease, median left ventricular ejection, left atrial size, and use of guideline-recommended ACE inhibitors and beta-blockers.

During up to 5 years of follow-up, the incidence of new-onset atrial fibrillation was 184 cases/1,000 person-years in the allopurinol users compared with 252/1,000 person-years in controls. In a Cox proportional hazards analysis adjusted for small differences in potential confounders, the use of allopurinol was independently associated with a 47% reduction in the risk of atrial fibrillation (P = .04), reported Dr. Hernandez of the University of Miami.

This intriguing finding needs to be confirmed in randomized prospective trials, he noted.

In a separate presentation, Dr. Benjamin R. Szwejkowski noted that left ventricular hypertrophy (LVH) is common in patients with type 2 diabetes and contributes to their elevated risk of cardiovascular morbidity and mortality.

Based on their hypothesis that LVH is related in part to oxidative stress and reducing that stress via xanthine oxidase inhibition using allopurinol can cause LVH regression, the investigators conducted a randomized, double-blind placebo-controlled clinical trial. Sixty-six patients with type 2 diabetes and echocardiographic evidence of LVH were randomized to allopurinol at 600 mg/day or placebo for 9 months.

The primary study endpoint was change in left ventricular mass between baseline and 9 months, as measured by cardiac MRI. Allopurinol resulted in a significant mean 2.65-g reduction in LV mass, while in the control group LV mass increased by 1.21 g. Similarly, LV mass indexed to body surface area fell significantly by 1.32 g/m2 in the allopurinol group while increasing by 0.65 g/m2 in the placebo arm, reported Dr. Szwejkowski of the University of Dundee(Scotland).

"Allopurinol may be a useful therapy to reduce cardiovascular risk in type 2 diabetic patients with LVH," according to the cardiologist.

Flow-mediated dilatation didn’t change significantly over time in either study group.

Dr. Szwejkowski and Dr. Hernandez reported having no relevant financial conflicts.

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