• Coronary Artery Disease Clinical Trials

Succinobucol (AGI-1067) is a novel compound believed to reduce inflammation in blood vessel walls. Jean-Claude Tardif, MD, of the Montreal Heart Institute gave an overview of the findings from the Phase 3 randomized, double-blind Aggressive Reduction of Inflammation Stops Events (ARISE) study. This study, conducted at 261 sites in the United States, Canada, South Africa, and the United Kingdom, compared succinobucol to placebo in 6,144 patients with acute coronary syndrome (ACS). Eligible patients had been hospitalized 14 to 365 days prior to study entry with an acute myocardial infarction (MI) or unstable angina. The primary endpoint of the study was a composite of cardiovascular (CV) death, resuscitated cardiac arrest, MI, stroke, unstable angina, or coronary revascularization.

There were no significant differences between the succinobucol 300 mg/day group (n=3,078) and the placebo group (n=3,066) in terms of baseline demographic variables. The study failed to meet its primary endpoint and the survival curves of the two treatment groups were virtually identical.

“The two Kaplan-Meier curves are almost super-imposed and in fact there was an almost identical number of primary events in both study groups. Basically the primary endpoint could not be more neutral than this,” commented Dr. Tardif. Heart failure hospitalizations were higher in the succinobucol group. Succinobucol also caused a significant rise in low density lipoprotein-cholesterol (LDL-C; p<0.0001) and a significant decrease in high density lipoprotein-cholesterol (HDL-C; p<0.0001).

In a secondary measure of combined athero-thrombotic endpoints including CV death, cardiac arrest, MI, and stroke, a significant decrease was observed with succinobucol therapy (hazard ratio=0.81; 95% CI, 0.68 to 0.98; p=0.028). Other secondary analyses indicated that the time to new onset of diabetes was significantly reduced in the succinobucol arm, a finding that was further supported by improvement in glycated hemoglobin A1c and glucose (all p<0.001 vs placebo).

Serious adverse event rates were similar between the two groups. The most common adverse event associated with succinobucol was diarrhea (23% vs 8% for placebo). Although the study did not meet its primary endpoint, the investigators remain optimistic about the future of the drug.

• © 2007 MD Conference Express