1. Clinical Trial Commentary
HOPE
SYMPHONY
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. Heart Outcomes Prevention Evaluation (HOPE)
ramipril vs placebo, n = 9541
Age > 55
CAD/CVA/PAD or DM + risk factors
no CHF/EF
267 hospitals in 19 countries
stopped 3/99 due to sig. death
only 3.3 mmHg SBP
vit. E no effect at 5 years (11.2 vs 11.1)

3. Heart Outcomes Prevention Evaluation (HOPE)
Placebo Ramipril OR p
(%) (%)
Mortality
CV Death
Stroke MI
MI, Stroke CV Death

4. Heart Outcomes Prevention Evaluation (HOPE)
Placebo Ramipril OR p
(%) (%)
Revasc
PTCA/CABG
CHF
New DM < 0.01

5. Primary endpoint (death/MI/SRI) at 90 days
SYMPHONY
Primary endpoint (death/MI/SRI) at 90 days 2 4 6 8 10 20 30 40 50 60 70 80 90
Days from Treatment Start
days from treatment start
ASA/Placebo
Sibrafiban LD
Sibrafiban HD
% of Pts, Death/MI/SRI
% of pts, death/MI/SRI
10.14%
10.07%
9.86%

6. Bleeding complications
ASA/Pl. LD Sib HD Sib
N = N = 3080 N = 3015
Major: Investigator 1.2% 1.7% 2.7% Algorithm 3.9% 5.2% 5.7%
Transfusion 4.7% 5.9% 6.5%
Minor: Investigator 4.5% 9.6% 15.9% Algorithm 12.6% % 24.6%

7. Meta-analysis of oral IIb/IIIa trials
Death
Trial N
Odds Ratio & 95% CI
Placebo
Fiban
EXCITE
1.36
7,232
1.0%
1.35%
Xemilofiban
OPUS
10,302
1.40
1.4%
1.95%
Orbofiban
SYMPHONY
9,169
1.12
1.8%
2.00%
Sibrafiban
Pooled
26,703
1.27
p = 0.023
1.4%
1.80%
0.5 1
1.5 2
p = Breslow-Day
homogeneity
Fiban Better
Placebo Better