The Reply

Abstract

We 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).1Sulfinpyrazone in the prevention of cardiac death after myocardial infarction. The Anturane Reinfarction Study.N Engl J Med. 1978; 298: 289-295Crossref PubMed Scopus (226) Google Scholar, 2The Anturane Trial Research GroupSulfinpyrazone in the prevention of sudden death after myocardial infarction.N Engl J Med. 1980; 302: 250-256Crossref PubMed Scopus (267) Google Scholar, 3Sulphinpyrazone in post-myocardial infarction. Report from the Anturan Reinfarction Italian Study.Lancet. 1982; 1: 237-242PubMed Google Scholar, 4The Anturane Reinfarction Trial reevaluation of outcome.N Engl J Med. 1982; 306: 1005-1008Crossref PubMed Scopus (36) Google Scholar 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.There are several other studies taking a similar approach to the question of SUA lowering for coronary heart disease risk reduction. For example, a recent study by Hoieggen et al suggests that losartan may be superior to atenolol for prevention of adverse cardiovascular outcomes in high-risk patients in the losartan intervention for endpoint-reduction in hypertension (LIFE) study due to its SUA lowering properties.5Hoieggen A.A.M. Kjeldsen S.E. Julius S. et al.The impact of serum uric acid on cardiovascular outcomes in the LIFE study.Kidney International. 2004; 65: 1041-1049Crossref PubMed Scopus (418) Google ScholarThe data from these studies may be misleading. Antiplatelet agents6Fox K.A. Mehta S.R. Peters R. et al.Clopidogrel in unstable angina to prevent recurrent ischemic events trial. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the cClopidogrel in unstable angina to prevent recurrent ischemic events (CURE) trial.Circulation. 2004; 110 (Sep 7; Epub 2004 Aug 16): 1202-1208Crossref PubMed Scopus (740) Google Scholar, 7Hung J. Medical Issues Committee of the National Heart Foundation of Australia. Aspirin for cardiovascular disease prevention.Med J Aust. 2003; 179 (Aug 4): 147-152PubMed Google Scholar and angiotensin receptor blockers8Weir R. McMurray J.J. Treatments that improve outcome in the patient with heart failure, left ventricular systolic dysfunction, or both after acute myocardial infarction.Heart. 2005; 91 (May; discussion ii31, ii43-8. Review): ii17-ii20Crossref PubMed Scopus (11) Google Scholar have both been shown to prevent adverse cardiovascular events in patients at high risk, including patients with recent MI. In both of these cases it is difficult to determine what benefit, if any, SUA lowering may have had on preventing adverse cardiovascular outcomes with the confounding other potential benefits of each therapy. Even xanthine oxidase inhibition might have benefits in cardiovascular disease prevention, independent of its ability to lower SUA levels.9Kinugasa Y. Ogino K. Furuse Y. et al.Allopurinol improves cardiac dysfunction after ischemia-reperfusion via reduction of oxidative stress in isolated perfused rat hearts.Circ J. 2003; 67 (Sep): 781-787Crossref PubMed Scopus (57) Google Scholar, 10Desco M.C. Asensi M. Marquez R. et al.Xanthine oxidase is involved in free radical production in type 1 diabetes protection by allopurinol.Diabetes. 2002; 51 (Apr): 1118-1124Crossref PubMed Scopus (333) Google Scholar, 11Cappola T.P.K.D. Nelson G.S. Berger R.D. et al.Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy.Circulation. 2001; 104: 2407-2411Crossref PubMed Scopus (377) Google Scholar, 12Struthers A.D.D.P. Lindsay P. McNaughton D. Broomhall J. Macdonald T.M. Effect of allopurinol on mortality and hospitalizations in congestive heart failure a retrospecctive cohort study.Heart. 2002; 87: 229-234Crossref PubMed Scopus (121) Google Scholar The question of whether SUA lowering itself is beneficial in high-risk patients may be difficult to answer definitively. We 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).1Sulfinpyrazone in the prevention of cardiac death after myocardial infarction. The Anturane Reinfarction Study.N Engl J Med. 1978; 298: 289-295Crossref PubMed Scopus (226) Google Scholar, 2The Anturane Trial Research GroupSulfinpyrazone in the prevention of sudden death after myocardial infarction.N Engl J Med. 1980; 302: 250-256Crossref PubMed Scopus (267) Google Scholar, 3Sulphinpyrazone in post-myocardial infarction. Report from the Anturan Reinfarction Italian Study.Lancet. 1982; 1: 237-242PubMed Google Scholar, 4The Anturane Reinfarction Trial reevaluation of outcome.N Engl J Med. 1982; 306: 1005-1008Crossref PubMed Scopus (36) Google Scholar 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. There are several other studies taking a similar approach to the question of SUA lowering for coronary heart disease risk reduction. For example, a recent study by Hoieggen et al suggests that losartan may be superior to atenolol for prevention of adverse cardiovascular outcomes in high-risk patients in the losartan intervention for endpoint-reduction in hypertension (LIFE) study due to its SUA lowering properties.5Hoieggen A.A.M. Kjeldsen S.E. Julius S. et al.The impact of serum uric acid on cardiovascular outcomes in the LIFE study.Kidney International. 2004; 65: 1041-1049Crossref PubMed Scopus (418) Google Scholar The data from these studies may be misleading. Antiplatelet agents6Fox K.A. Mehta S.R. Peters R. et al.Clopidogrel in unstable angina to prevent recurrent ischemic events trial. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the cClopidogrel in unstable angina to prevent recurrent ischemic events (CURE) trial.Circulation. 2004; 110 (Sep 7; Epub 2004 Aug 16): 1202-1208Crossref PubMed Scopus (740) Google Scholar, 7Hung J. Medical Issues Committee of the National Heart Foundation of Australia. Aspirin for cardiovascular disease prevention.Med J Aust. 2003; 179 (Aug 4): 147-152PubMed Google Scholar and angiotensin receptor blockers8Weir R. McMurray J.J. Treatments that improve outcome in the patient with heart failure, left ventricular systolic dysfunction, or both after acute myocardial infarction.Heart. 2005; 91 (May; discussion ii31, ii43-8. Review): ii17-ii20Crossref PubMed Scopus (11) Google Scholar have both been shown to prevent adverse cardiovascular events in patients at high risk, including patients with recent MI. In both of these cases it is difficult to determine what benefit, if any, SUA lowering may have had on preventing adverse cardiovascular outcomes with the confounding other potential benefits of each therapy. Even xanthine oxidase inhibition might have benefits in cardiovascular disease prevention, independent of its ability to lower SUA levels.9Kinugasa Y. Ogino K. Furuse Y. et al.Allopurinol improves cardiac dysfunction after ischemia-reperfusion via reduction of oxidative stress in isolated perfused rat hearts.Circ J. 2003; 67 (Sep): 781-787Crossref PubMed Scopus (57) Google Scholar, 10Desco M.C. Asensi M. Marquez R. et al.Xanthine oxidase is involved in free radical production in type 1 diabetes protection by allopurinol.Diabetes. 2002; 51 (Apr): 1118-1124Crossref PubMed Scopus (333) Google Scholar, 11Cappola T.P.K.D. Nelson G.S. Berger R.D. et al.Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy.Circulation. 2001; 104: 2407-2411Crossref PubMed Scopus (377) Google Scholar, 12Struthers A.D.D.P. Lindsay P. McNaughton D. Broomhall J. Macdonald T.M. Effect of allopurinol on mortality and hospitalizations in congestive heart failure a retrospecctive cohort study.Heart. 2002; 87: 229-234Crossref PubMed Scopus (121) Google Scholar The question of whether SUA lowering itself is beneficial in high-risk patients may be difficult to answer definitively. Clinical Trials of Uric Acid Lowering for Coronary Heart Disease Risk ReductionThe American Journal of MedicineVol. 119Issue 4PreviewBaker et al. reviewed the scientific literature on the relation of serum uric acid to cardiovascular disease published since 1998.1 In concluding, they note that “there is sufficient evidence … to justify a large-scale controlled trial (of uric acid lowering) in high-risk individuals.” Full-Text PDF