Principal Findings:

This was an event-driven trial, which was terminated early due to futility. At this time, a total of 15,871 patients were randomized at 935 sites in 27 countries, 7,933 to dalcetrapib and 7,938 to placebo. About 24% had diabetes mellitus, 68% had hypertension, and 63% met criteria for the metabolic syndrome. About 85% of patients presented with biomarker-positive ACS, with a mean time from index hospitalization to randomization of 61 days. Revascularization was undertaken in 91% of patients. The mean baseline low-density lipoprotein (LDL) and HDL cholesterol values were 76 and 42 mg/dl, respectively. Median baseline high-sensitivity C-reactive protein (hs-CRP) was 1.5 mg/L.

Dalcetrapib resulted in a 30% increase in HDL cholesterol as compared with placebo, with a negligible effect on LDL cholesterol. Triglycerides increased by approximately the same amount in both arms (10%). Apolipoprotein A1 levels were increased by 10% after 3 months of treatment with dalcetrapib. The primary outcome of coronary heart disease death, nonfatal myocardial infarction (MI), ischemic stroke, hospitalization for unstable angina, and resuscitated cardiac arrest was similar between the dalcetrapib and placebo arms at 3 years (8.3% vs. 8.0%, hazard ratio 1.04; 95% confidence interval 0.93-1.16, p = 0.52). Individual outcomes including coronary heart disease death (1.5% vs. 1.6%, p = 0.66), nonfatal MI (5.2% vs. 5.1%, p = 0.80), all-cause mortality (2.8% vs. 2.9%, p = 0.90), coronary revascularization (8.5% vs. 8.5%, p = 0.97), and ischemic stroke (1.1% vs. 0.9%, p = 0.16) were similar between the two arms. Systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo over the duration of follow-up (p < 0.0001), although no differences were noted in plasma aldosterone, bicarbonate, or K levels. At 3 months, median hs-CRP was also higher in the dalcetrapib arm by 0.2 mg/dl (p < 0.001).