European Society of Cardiology

European Society of Cardiology

Perspective from Andrew Kates, MD, FACC
August 29, 2017
3 min read

REVEAL: CETP inhibitor added to statin lowers incidence of major coronary events

Perspective from Andrew Kates, MD, FACC
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Incidence of major coronary events was significantly reduced among patients with atherosclerotic vascular disease who received statin therapy with the addition of the cholesterol ester transfer protein inhibitor anacetrapib, according to data presented at the European Society of Cardiology Congress.

The findings, which compared statin therapy plus anacetrapib (Merck) to statin therapy plus placebo, were simultaneously published in The New England Journal of Medicine.

Merck stated in a press release that it is “reviewing the results of the trial with external experts and will consider whether to file new drug applications with the [FDA] and other regulatory agencies.”

“Pharmacological inhibition of cholesterol ester transfer protein (CETP) can produce substantial increases in HDL cholesterol levels, along with reductions in levels of non-HDL cholesterol,” Louise Bowman, MD, FRCP, associate professor at the Clinical Trial Service Unit of the University of Oxford and colleagues wrote in the study. “However, previous randomized clinical outcomes trials of CETP inhibitor therapy were stopped after approximately 2 years of follow-up because of either hazards associated with the therapy or an apparent lack of efficacy.”

Researchers conducted the double-blind, placebo-controlled, phase 3 REVEAL trial to assess the clinical efficacy and safety of anacetrapib in patients with preexisting atherosclerotic vascular disease who were receiving effective therapy with atorvastatin and had a mean LDL cholesterol level of 61 mg/dL, a mean non-HDL cholesterol level of 92 mg/dL and a mean HDL cholesterol level of 40 mg/dL.

A total of 30,449 patients were assigned to receive 100 mg of anacetrapib once daily or matching placebo.

The prespecified primary outcome of the study was the first major coronary event, a composite of coronary death, MI or coronary revascularization. Median follow-up was 4.1 years.

The occurrence of the primary outcome was significantly less frequent among patients in the anacetrapib group compared with the placebo group (10.8% vs. 11.8%; RR = 0.91; 95% CI, 0.85-0.97), Bowman and colleagues found.

Relative difference in risk was consistent across multiple prespecified groups, according to the researchers.

The mean HDL level was higher at by 43 mg/dL and the mean level of non-HDL was lower by 17 mg/dL in the anacetrapib group compared with the placebo group.

The groups did not differ in risk for death, cancer, or other adverse events, according to the researchers.

“During a median of 4 years of follow-up, anacetrapib treatment was not associated with any of the previously hypothesized adverse effects of very low levels of cholesterol (eg, reduced cognitive function, increased cancer incidence or nonvascular death),” the researchers wrote. “We found that the addition of CETP inhibitor anacetrapib to intensive statin treatment in patients with atherosclerotic vascular disease resulted in a significantly lower incidence of major coronary events than the addition of placebo during 4 years of treatment.”


Landray M, et al. Hot Line: Late Breaking Clinical Trials 4. Presented at: European Society of Cardiology Congress; August 26-30, 2017; Barcelona, Spain.

Bowman L, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1706444.

Disclosure: The study was supported in part by Merck. Bowman reports receiving grants from Merck. Please see the full study for a list of the other authors’ relevant financial disclosures.