Clinical Trials of Uric Acid Lowering for Coronary Heart Disease Risk Reduction

Abstract

Baker et al. reviewed the scientific literature on the relation of serum uric acid to cardiovascular disease published since 1998.1Baker J.F. Krishnan E. Chen L. Schumacher H.R. Serum uric acid and cardiovascular disease recent developments, where do they leave us?.Am J Med. 2005; 118: 816-826Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar In concluding, they note that “there is sufficient evidence … to justify a large-scale controlled trial (of uric acid lowering) in high-risk individuals.” Three secondary coronary heart disease (CHD) prevention trials have been published in which patients were randomly allocated to uric acid-lowering treatment. The Anturane Reinfarction Trial2Sulfinpyrazone in the prevention of cardiac death after myocardial infarction. The Anturane Reinfarction Study.N Engl J Med M. 1978; 298: 289-295Crossref PubMed Scopus (226) Google Scholar, 3The Anturane Trial Research GroupSulfinpyrazone in the prevention of sudden death after myocardial infarction.N Engl J Med. 1980; 302: 250-256Crossref PubMed Scopus (266) Google Scholar and the Anturan Reinfarction Italian Study4Sulphinpyrazone in post-myocardial infarction. Report from the Anturan Reinfarction Italian Study.Lancet. 1982; 1: 237-242PubMed Google Scholar both reported large statistically significant decreases in the risk for sudden cardiac death among patients with myocardial infarction who were treated with sulfinpyrazone, an antiplatelet uricosuric agent. Although serum uric acid levels were measured, they were not reported in the Anturane Reinfarction Trial except to note that participants taking sulfinpyrazone had consistent lowering of serum uric acid levels.2Sulfinpyrazone in the prevention of cardiac death after myocardial infarction. The Anturane Reinfarction Study.N Engl J Med M. 1978; 298: 289-295Crossref PubMed Scopus (226) Google Scholar The results of the Anturane Reinfarction Trial were questioned but were subsequently affirmed by an independent committee of adjudicators.5The Anturane Reinfarction Trial. reevaluation of outcome.N Engl J Med. 1982; 306: 1005-1008Crossref PubMed Scopus (36) Google Scholar The Anturan Reinfarction Italian Study, another secondary CHD prevention trial, reported that treatment with sulfinpyrazone resulted in a marked reduction in fatal and nonfatal myocardial infarctions.4Sulphinpyrazone in post-myocardial infarction. Report from the Anturan Reinfarction Italian Study.Lancet. 1982; 1: 237-242PubMed Google Scholar Serum uric acid levels were measured as a means of assessing pill compliance, and on-study serum uric acid levels were reported as 2.8 mg/dL in the sulfinpyrazone group, compared with 5.5 mg/dL in the placebo group. In contrast with these 2 positive studies, a Canadian trial using sulfinpyrazone in patients hospitalized for unstable angina reported no benefit on the risk for cardiac death and nonfatal myocardial infarction.6Cairns J.A. Gent M. Singer J. et al.Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial.N Engl J Med. 1985; 313: 1369-1375Crossref PubMed Scopus (894) Google Scholar Although each of these studies examined sulfinpyrazone as an antiplatelet agent, they effectively tested whether lowering serum uric acid levels with a uricosuric agent decreases CHD events. The ReplyThe American Journal of MedicineVol. 119Issue 4PreviewWe thank Dr. Simon for his comments. He cites several studies evaluating the uricosuric antiplatelet agent, sulfinpyrazone, in the prevention of reinfarction in patients with myocardial infarction (MI).1-4 He notes that these studies demonstrate that patients treated with sulfinpyrazone had significantly lower serum uric acid (SUA) levels, as well as fewer subsequent coronary events. We agree that these studies are of interest, but we have concerns about attributing this effect specifically to uric acid lowering. Full-Text PDF