Impact of Oxypurinol in Patients With Symptomatic Heart Failure
Open accessAbstract
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 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).
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Subsequent larger trials with allopurinol/oxypurinol failed to report substantial positive effects compared with placebo.
“Despite these initial results, subsequent trials with larger number of patients have failed to report substantial positive effects as compared with the placebo groups (361, 405), although the meta-analysis of available studies indicates some improvement of cardiovascular function (430).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [405]
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- Authors
- 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.
- Affiliations
- University of Miami (US)
- Cardiome (Canada) (CA)
- Rutgers, The State University of New Jersey (US)
- Boston University (US)
- Toronto General Hospital (CA)
- Brigham and Women's Hospital (US)
- Corresponding author
- Hare, Joshua M.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 51
- Issue
- 24
- Pages
- 2301-2309
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1414418298
- Cited by
- 392
- References
- 25
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 18 · 2023: 21 · 2022: 21 · 2021: 18 · 2020: 34 · 2019: 33 · 2018: 20 · 2017: 8 · 2016: 23 · 2015: 16 · 2014: 26 · 2013: 18 · 2012: 41
- FWCI
- 21.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- oxypurinol, xanthine oxidase inhibition, heart failure, systolic dysfunction, serum uric acid, hyperuricemia, biomarkers, quality of life
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Double-Blind Method, Enzyme Inhibitors, Female, Health Status Indicators, Heart Failure, Humans, Male, Middle Aged, Oxypurinol, Quality of Life, Surveys and Questionnaires, Systole, Uric Acid, Xanthine Oxidase, Natriuretic Peptide, Brain
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