ARISE Trial Aggressive Reduction of Inflammation Stops Events Presented at the American College of Cardiology Annual Scientific Session March, 2007 Presented by Dr. Jean-Claude Tardif

ARISE Trial: Background The goal of the trial was to evaluate treatment with the novel antioxidant agent succinobucol compared with placebo among high-risk patients with recent acute coronary syndrome (ACS). ACC 2007

ARISE Trial: Study Design 6144 patients hospitalized for acute myocardial infarction (MI) or unstable angina in the prior 14-365 days and either 1) age > 60 yrs; 2) diabetes; or 3) age > 55 yrs with > 1 risk factor Randomized. Double-blinded. Placebo-controlled. Mean follow-up 24 months Mean age 65 yrs. 28% female. R 14-day placebo run-in phase Succinobucol (300mg/day) n=3078 Placebo n=3066 24 mos. follow-up Primary Endpoint: Composite of cardiovascular (CV) death, cardiac arrest, MI, stroke, unstable angina or coronary revascularization. Secondary Endpoint: Primary endpoint plus all cause death; primary endpoint without coronary revascularization; primary endpoint without unstable angina or coronary revascularization (CV death, cardiac arrest, MI or stroke). ACC 2007

ARISE Trial: Primary Endpoint Composite of CV death, cardiac arrest, MI, stroke, unstable angina or coronary revascularization There was no difference in the primary composite endpoint between treatment groups (17.2% for succinobucol vs. 17.3% for placebo, hazard ratio (HR) 1.00, p-0.985). p = 0.985 Composite endpoint (%) n = 3078 n = 3066 ACC 2007

ARISE Trial: Secondary Endpoint Composite of CV death, cardiac arrest, MI or stroke p = 0.028 The secondary endpoint of CV death, cardiac arrest, MI or stroke was lower with succinobucol than placebo (6.7% vs. 8.2%, HR 0.81, p=0.028). Composite endpoint (%) n = 3078 n = 3066 ACC 2007

ARISE Trial: Results New onset diabetes was lower in the succinobucol group (1.6% vs. 4.2%, p<0.0001). Heart failure occurred more frequently in the succinobucol arm (n=107 vs. n=83). Serious adverse events occurred with similar frequency between groups (31% with succinobucol vs. 29% with placebo). ACC 2007

ARISE Trial: Summary Among high-risk patients with recent ACS, treatment with the novel antioxidant agent succinobucol was not associated with a difference in the primary endpoint of CV death, cardiac arrest, MI, stroke, unstable angina or coronary revascularization compared with placebo at 2 year follow-up. ACC 2007

ARISE Trial: Summary While some endpoints such as the new onset diabetes and the composite of CV death, cardiac arrest, MI, and stroke were in favor of succinobucol, others such as heart failure and unstable angina showed higher event rates with succinobucol. With the exception of an increase in heart failure, succinobucol appeared safe. Further data would be required to see if the reduction in the atherosclerotic endpoint with succinobucol despite an increase in LDL can be confirmed. ACC 2007