Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease.

Abstract

BACKGROUND:

The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease.

METHODS:

In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.

RESULTS:

At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91).

CONCLUSIONS:

Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).

• Authors: A Michael Lincoff, Stephen J Nicholls, Jeffrey S Riesmeyer, Philip J Barter, H Bryan Brewer, Keith A A Fox, C Michael Gibson, Christopher Granger, Venu Menon, Gilles Montalescot, Daniel Rader, Alan R Tall, Ellen McErlean, Kathy Wolski, Giacomo Ruotolo, Burkhard Vangerow, Govinda Weerakkody, Shaun G Goodman, Diego Conde, Darren K McGuire, Jose C Nicolau, Jose L Leiva-Pons, Yves Pesant, Weimin Li, David Kandath, Simon Kouz, Naeem Tahirkheli, Denise Mason, Steven E Nissen, ACCELERATE Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 376 Issue 20 Pg. 1933-1942 (05 18 2017) ISSN: 1533-4406 [Electronic] United States
• PMID: 28514624 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Anticholesteremic Agents
• Biomarkers
• Cholesterol Ester Transfer Proteins
• Cholesterol, HDL
• Cholesterol, LDL
• Benzodiazepines
• evacetrapib

Topics

• Aged
• Anticholesteremic Agents (adverse effects, therapeutic use)
• Benzodiazepines (adverse effects, therapeutic use)
• Biomarkers (blood)
• Cardiovascular Diseases (blood, drug therapy, prevention & control)
• Cholesterol Ester Transfer Proteins (antagonists & inhibitors)
• Cholesterol, HDL (blood)
• Cholesterol, LDL (blood)
• Diabetes Mellitus (drug therapy)
• Double-Blind Method
• Female
• Humans
• Intracranial Arteriosclerosis (drug therapy)
• Male
• Middle Aged
• Myocardial Ischemia (drug therapy)
• Peripheral Vascular Diseases (drug therapy)
• Risk
• Treatment Failure