1. 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

2. 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 mg BID
primary end point: all-cause mortality

3. 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

4. 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

5. 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 IU)
primary end point: all-cause mortality

6. 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

7. 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

8. PURSUIT trial
Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy
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