Although it decreased low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C), evacetrapib failed to reduce major adverse cardiovascular events (MACE) when compared with placebo in high vascular risk patients.

Stephen J. Nicholls, MBBS, PhD, of the Cleveland Clinic, presented the findings of the ACCELERATE trial at the 2016 American College of Cardiology Scientific Sessions & Expo

During a press conference, Dr Nicholls said that for more than a decade, there has been a lot of interest in inhibiting cholesteryl ester transfer protein (CETP), originally with the concept that it would be a profound HDL-C raiser.

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“Along the journey, we have appreciated that it lowers LDL as well,” he said. “We have animal and genetic data that having less CETP is a good thing, although there have been 2 CETP inhibitors that have gone before evacetrapib with disappointing results in clinical trials… So we brought evacetrapib to phase 3 having done phase 2 studies [demonstrating] robust HDL raising, LDL lowering on top of a statin.”                                                                                                            

The phase 3, multicenter, double blind, randomized trial included 12 092 patients at high vascular risk. Researchers defined high vascular risk as: an acute coronary syndrome within the previous 30 to 365 days; cerebrovascular atherosclerotic disease; peripheral vascular disease; or diabetes with coronary artery disease.

Patients (77% male; age: 65 years) were randomly assigned 1:1 to either 130 mg evacetrapib (n=6038), a CETP inhibitor, or placebo (n=6054) for at least 1.5 years. Baseline clinical characteristics were well matched between groups. 

Time to first event of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization served as the primary end point.

According to Dr Nicholls, the trial was stopped prematurely in October 2015 for clinical futility on the recommendation of the data monitoring committee. 

“We’ve presented the results today of 99% of the patients who have completed their end of study visit just prior to database lock,” Dr Nicholls said.

Those results suggested that compared with placebo, patients who received evacetrapib demonstrated a 130% increase in HDL-C (104 mg/dL vs 46 mg/dL) and a 37% drop in LDL-C (55 mg/dL vs 84 mg/dL). 

Despite these findings, the primary end point was nearly identical in the 2 groups (evacetrapib, 12.8% vs placebo, 12.7%; hazard ratio [HR]:1.01; P=.85).

In addition, there were no significant reductions in any of the component end points. However, there was a trend toward a lower rate of all-cause mortality in the evacetrapib group (3.8% vs 4.1%; HR:0.84; P=.06), which the researchers believe was a chance finding. 

“This [study] really reflects why we do these clinical trials, because the numbers looked better, but at the end of the day, it is the clinical event that counts, and we see no benefit here,” Dr Nicholls said.

He added that the investigators have become increasingly skeptical as to whether CETP inhibitors will be of use in these high-risk patients.

“There is another study that is ongoing. It will be interesting to see what the results of that are,” Dr Nicholls said. “We would like to open the database to independent investigators to ask really important scientific questions, so we are putting together a process … to enable for that to happen.”


  1. Nicholls SJ, Lincoff A, Barter P, et al. Late-Breaking Clinical Trials II. The ACCELERATE trial: impact of the cholesteryl ester transfer protein inhibitor evacetrapib on cardiovascular outcome. Presented at the 65th Annual Scientific Session and Expo of the American College of Cardiology. April 2-4, 2016; Chicago, IL.

This article originally appeared on The Cardiology Advisor