CETP-inhibitor does not reduce CV events

Stephen J. Nicholls (University of Adelaide, Australia)

Presented at ACC 2016

Background

The potent cholesteryl ester transfer protein (CETP) inhibitor evacetrapib has been demonstrated to raise high-density lipoprotein cholesterol (HDL-C) by 54-129%, reduce low-density lipoprotein cholesterol (LDL-C) by 14-36% and enhance cellular cholesterol efflux capacity. The ACCELERATE trial
aimed to determine the impact of evacetrapib on major adverse cardiovascular outcomes in patients with high risk vascular disease. ACCELERATE was a phase 3, multicenter, randomized, double-blind trial in which 12,092 patients with either an acute coronary syndrome within the prior 30-365 days, cerebrovascular atherosclerotic disease, peripheral vascular disease or diabetes with coronary artery disease were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy for at least 1.5 years.
The primary efficacy endpoint was the time to first event of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization.

Main results

• LDL-C levels were lowered with 37% in patients on evacetrapib, compared with placebo
• HDL-C levels were increased by 130% in patients on evacetrapib, compared with patients taking a placebo.
• However, there was no difference between the two groups in terms of the study’s primary endpoint (12.8% for evacetrapib vs. 12.7% for placebo; HR 1.01, 95% CI 0.91-1.12, P=0.85)
• A borderline significant reduction in all-cause mortality was observed in the evacetrapib group (3.8% vs. 4.1%; HR 0.84, 95% CI 0.71-1.01, P=0.06)
• The results raised no safety concerns for evacetrapib and did not reveal any major side effects.

Conclusion

Administration of the CETP inhibitor evacetrapib did not reduce the rate of cardiovascular events in high risk vascular patients despite demonstrating favourable effects on established cardiovascular biomarkers. The findings continue to challenge the hope that CETP inhibition might successfully address residual CV risk.

Source

Press release ACC 2016, 3 April 2016