Febuxostat increases cardiovascular mortality in CARES trial

ORLANDO – Long-term treatment with febuxostat in gout patients with comorbid cardiovascular disease conferred significantly higher risks of both cardiovascular death and all-cause mortality, compared with allopurinol, in the Food and Drug Administration–mandated postmarketing CARES trial, William B. White, MD, reported at the annual meeting of the American College of Cardiology.

CARES (Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout and Cardiovascular Disease) was a prospective, double-blind, 320-center North American clinical trial in which 6,190 patients were randomized to febuxostat (Uloric) at 40-80 mg once daily or 200-600 mg of allopurinol once daily. The postmarketing safety study was required by the FDA as a condition of marketing approval for febuxostat in light of preapproval evidence suggestive of a possible increased risk of cardiovascular events, explained Dr. White, professor of medicine and chief of the division of hypertension and clinical pharmacology at the University of Connecticut, Farmington.

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The primary study endpoint was a composite of cardiovascular death, MI, stroke, and unstable angina resulting in urgent revascularization. In a modified intention-to-treat analysis at a median of 32 and maximum of 85 months of follow-up, the rate was 10.8% in the febuxostat group and similar at 10.4% in the allopurinol group. So there was no safety issue there.