Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study.
OBJECTIVE
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 approximately 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).
The University of Miami Miller School of Medicine, Miami, Florida v, USA. jhare@med.miami.edu
Joshua M
JM
Hare
Brian
B
Mangal
Joanne
J
Brown
Charles
C
Fisher
Ronald
R
Freudenberger
Wilson S
WS
Colucci
Douglas L
DL
Mann
Peter
P
Liu
Michael M
MM
Givertz
Richard P
RP
Schwarz
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006305:Health Status Indicators; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000187:drug effects; D010117:Oxypurinol / Q000494:pharmacology / Q000627:therapeutic use*; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013599:Systole / Q000187:drug effects; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D020097:Natriuretic Peptide, Brain; D014527:Uric Acid; D014969:Xanthine Oxidase; D010117:Oxypurinol