Clinical Trial Commentary BEST CHAMP Dr Eric Topol Chairman and Professor, Department of Cardiology Director of the Joseph J Jacobs Center for Thrombosis and Vascular Biology at the Cleveland Clinic Dr Robert Califf Professor of Cardiology Associate Vice Chancellor for Clinical Research at Duke University

Beta-blockers Evaluation Survival Trial Methodology to evaluate the addition of beta-blockers in patients with severe heart failure inclusion criteria (n=2 708): age > 18 years NYHA class III-IV heart failure LVEF < 35% patients on ACE inhibitors bucindolol vs placebo 3 mg , titrated up to 50-100 mg BID primary end point: all-cause mortality

BEST trial Results mean follow-up planned for 3 years study terminated after 2 years (positive result was not expected) Table 1: BEST outcomes bucindolol placebo p value all-cause mortality 30.2% 33% NS cardiovascular deaths* 24.4% 27.9% p=0.04 *due to CHF, sudden death or MI

BEST trial Conclusions bucindolol did not provide a survival benefit in the population as a whole a trend towards benefit was seen in patients with NYHA class III symptoms no benefit with bucindolol was seen in class IV patients no benefit with bucindolol was seen in African-American patients

Combination Hemotherapy and Mortality Prevention Methodology to demonstrate a 15% reduction in all-cause mortality in survivors of acute MI on ASA/warfarin vs ASA alone open-label trial (n=5 059) patients randomized within 14 days of infarct to: ASA 162 mg qd or ASA 81 mg qd + warfarin (INR 1.5-2.5 IU) primary end point: all-cause mortality

CHAMP trial Results mean age 62 years (99% men) no difference in all-cause mortality between the 2 groups no difference in cardiovascular mortality, stroke, nonfatal MI higher incidence of major bleeding (but not fatal, intracranial) in combination arm (p<0.001) bleeding risk increased with age in both groups

CHAMP trial Conclusions no survival advantage to the addition of warfarin to ASA after acute MI major hemorrhage rates low in both groups, although combination therapy was associated with a 2-fold increase in primarily GI hemorrhages intracranial or fatal hemorrhages not increased in combination therapy group

PURSUIT trial Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy 10 987 patients with acute coronary syndromes (non-ST elevation) enrolled treated with eptifibatide vs placebo (in addition to conventional therapy) patients treated with eptifibatide had a significant reduction in death or MI (p=0.025) at 30-day endpoint The PURSUIT Trial investigators. N Engl J Med 1998;339:436-43