Experimental cholesterol drug failed to prevent cardiovascular events

Phase III trial halted early as treatment did not reduce rate of vascular events in patients with high-risk disease.

3D render of the cholesterol ester transfer protein inhibitor, evacetrapib

In phase II trials, the cholesterol ester transfer protein inhibitor, evacetrapib, increased high-density lipoprotein (HDL) cholesterol levels by up to 130% and reduced low-density lipoprotein (LDL) cholesterol by up to 35%, but it was unknown if this translated to an effect on cardiovascular outcomes.

In a phase III trial, 12,092 patients with high-risk cardiovascular disease were randomly assigned to 130mg dose of evacetrapib or placebo for two years.

The trial was stopped after a median follow-up of 28 months owing to futility. At this point, the primary endpoint (death from cardiovascular causes, myocardial infarction, stroke, coronary revascularisation, or hospitalisation for unstable angina) had occurred in 12.9% of the evacetrapib group and 12.8% of the placebo group (hazard ratio 1.01; 95% confidence interval 0.91–1.11; P=0.91).

Reporting in The New England Journal of Medicine
(online, 18 May 2017), the researchers say the results reinforce the need for adequately powered clinical trials of new agents, even when results have been seen with surrogate endpoints.


[1] Lincoff AM, Nicholls S, Riesmeyer J et al. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N Engl J Med 2017;376:1933–1942. doi: 10.1056/NEJMoa1609581

Last updated
Clinical Pharmacist, CP June 2017 online;9(6):DOI:10.1211/PJ.2017.20203054

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