Impact of Oxypurinol in Patients With Symptomatic Heart Failure. Results of the OPT-CHF Study

Joshua M. Hare, Brian Mangal, Joanne Brown, Charles Fisher, Ronald Freudenberger, Wilson S. Colucci, Douglas L. Mann, Peter Liu, Michael M. Givertz, Richard P. Schwarz

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265 Scopus citations

Abstract

Objectives: This study evaluated whether a xanthine oxidase (XO) inhibitor, oxypurinol, produces clinical benefits in patients with New York Heart Association functional class III to IV heart failure due to systolic dysfunction receiving optimal medical therapy. Background: Increased XO activity may contribute to heart failure pathophysiology. Methods: Patients (n = 405) were randomized to oxypurinol (600 mg/day) or placebo. Efficacy at 24 weeks was assessed using a composite end point comprising heart failure morbidity, mortality, and quality of life. Results: The percentage of patients characterized as improved, unchanged, or worsened did not differ between those receiving oxypurinol or placebo. Oxypurinol reduced serum uric acid (SUA) by ∼2 mg/dl (p < 0.001). In a subgroup analysis, patients with elevated SUA (>9.5 mg/dl, n = 108) responded favorably to oxypurinol (p = 0.02 for interaction term), whereas oxypurinol patients with SUA <9.5 mg/dl exhibited a trend towards worsening. In addition, SUA reduction to oxypurinol correlated with favorable clinical response. Within the entire oxypurinol patient cohort, those characterized as either improved or unchanged had significantly greater reductions in SUA compared with patients who worsened (-2.3 ± 2.1 mg/dl vs. -1.0 ± 1.9 mg/dl, p = 0.0006). In placebo patients, lower baseline SUA, but not change in SUA, correlated with improved clinical outcome. Conclusions: Oxypurinol did not produce clinical improvements in unselected patients with moderate-to-severe heart failure. However, post-hoc analysis suggests that benefits occur in patients with elevated SUA in a manner correlating with the degree of SUA reduction. Serum uric acid may serve as a valuable biomarker to target XO inhibition in heart failure. (Oxypurinol Compared With Placebo for Class III-IV NYHA Congestive Heart Failure; NCT00063687).

Original languageEnglish
Pages (from-to)2301-2309
Number of pages9
JournalJournal of the American College of Cardiology
Volume51
Issue number24
DOIs
StatePublished - Jun 17 2008
Externally publishedYes

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    Hare, J. M., Mangal, B., Brown, J., Fisher, C., Freudenberger, R., Colucci, W. S., Mann, D. L., Liu, P., Givertz, M. M., & Schwarz, R. P. (2008). Impact of Oxypurinol in Patients With Symptomatic Heart Failure. Results of the OPT-CHF Study. Journal of the American College of Cardiology, 51(24), 2301-2309. https://doi.org/10.1016/j.jacc.2008.01.068