REVEAL: anacetrapib cuts major coronary events by 9% in 30,449 patients already on intensive statin therapy (N Engl J Med 2017)

Original title: Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

N Engl J Med · 28 August 2017 · 9

HPS3/TIMI55–REVEAL Collaborative Group, Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, Collins R, Wiviott SD, Cannon CP, Braunwald E, Sammons E, Landray MJ

REVEAL randomised 30,449 adults with atherosclerotic vascular disease already receiving intensive atorvastatin therapy (mean LDL-C 61 mg/dL, non-HDL-C 92 mg/dL, HDL-C 40 mg/dL) to anacetrapib 100 mg daily (15,225 patients) or matching placebo (15,224 patients). Over a median 4.1-year follow-up, the primary outcome, a composite of coronary death, myocardial infarction or coronary revascularisation, occurred in significantly fewer anacetrapib patients (10.8% versus 11.8%; rate ratio 0.91, 95% CI, 0.85 to 0.97, P=0.004), consistent across prespecified subgroups. At the trial midpoint, HDL cholesterol was 43 mg/dL higher (a 104% relative difference) and non-HDL cholesterol 17 mg/dL lower (-18%) with anacetrapib, with no significant between-group differences in death, cancer or other serious adverse events. The authors conclude that in statin-treated patients with atherosclerotic vascular disease, anacetrapib reduced major coronary events versus placebo, the pivotal trial establishing the first clear cardiovascular benefit for CETP inhibition, funded by Merck and others.

Original abstract

Background: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.

Results: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.

Conclusions: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .).

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.