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EXACT-HF: Allopurinol fails to improve outcomes in hyperuricemic HF
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At 24 weeks, xanthine oxidase inhibition with allopurinol did not improve clinical status, exercise capacity, quality of life or left ventricular ejection fraction in high-risk patients with HF, decreased ejection fraction and elevated levels of uric acid, according to results of the EXACT-HF study.
The randomized, double blind, multicenter study included 253 patients with LVEF of 40% or less and serum uric acid of at least 9.5 mg/dL. The median age of the cohort was 63 years and the median LVEF was 25%. Common comorbidities included diabetes, hypertension, and atrial fibrillation or atrial flutter.
The researchers randomly assigned each patient to allopurinol at a target dose of 600 mg daily or placebo.
The primary endpoint was a composite of survival, worsening HF and patient global evaluation at 24 weeks.
Compared with placebo, the allopurinol group had significantly reduced serum uric acid at 12 weeks (treatment difference, –4.2; P < .0001) and at 24 weeks (treatment difference, –3.5; P < .0001). The researchers observed no significant difference in clinical status at 24 weeks; clinical status was worsened in 45% of the allopurinol group vs. 46% of the placebo group, unchanged in 42% vs. 34% and improved in 13% vs. 19% (P = .68).
In addition, the treatment groups did not differ at 12 and 24 weeks in Kansas City Cardiomyopathy Questionnaire score or 6-minute walk distance.
The researchers observed no change in LVEF in either group or between the two groups.
The prevalence of rash was higher in the allopurinol group (10% vs. 2%; P = .01), but rates of serious adverse events were similar with allopurinol or placebo (20% allopurinol vs. 15% placebo; P = .36).
According to the researchers, these findings contradict a growing body of evidence that supports the promise of xanthine oxidase inhibition for the treatment of patients with HF.
“Despite accumulating evidence of the potential efficacy and safety of xanthine oxidase inhibition in cardiovascular disease states, in general, and HF, in particular, we found no clinical benefit of high-dose allopurinol in patients with HF, reduced ejection fraction and elevated [uric acid] levels at 24 weeks,” the researchers wrote. “For patients at high risk of HF events, alternative therapies are needed.” – by Jennifer Byrne
Disclosure: The researchers report no relevant financial disclosures.
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