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

https://doi.org/10.1016/j.jacc.2008.01.068Get rights and content
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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)

Abbreviations and Acronyms

BNP
brain natriuretic peptide
CCE
composite clinical end point
CI
confidence interval
CV
cardiovascular
ITT
intent to treat
MLHF
Minnesota Living with Heart Failure
NYHA
New York Heart Association
PGHFCS
Patient Global Heart Failure Clinical Status
SUA
serum uric acid
XO
xanthine oxidase

Cited by (0)

This study was funded by Cardiome Pharma Corp., Vancouver, British Columbia, Canada. Brian Mangal, Joanne Brown, and Dr. Fisher are employees of Cardiome Pharma Corp. Dr. Hare is a consultant to Cardiome Pharma Corp.