REVEAL extended follow-up: the coronary benefit of anacetrapib grows over time, 12% overall, with no long-term safety signal (Eur Heart J 2022)

Original title: Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease

Eur Heart J · 6 April 2022 · 9

HPS3/TIMI55-REVEAL Collaborative Group, Writing Committee, Sammons E, Hopewell JC, Chen F, Stevens W, Wallendszus K, Valdes-Marquez E, Dayanandan R, Knott C, Murphy K, Wincott E et al.

REVEAL was the first trial to show that adding a CETP inhibitor to intensive statin therapy reduces major coronary events. This paper reports extended follow-up beyond the scheduled treatment period for the 30 449 participants with prior atherosclerotic vascular disease randomised to anacetrapib 100 mg daily or placebo on top of open-label atorvastatin, of whom 26 129 survivors entered a blinded post-trial follow-up after treatment stopped. Anacetrapib produced a 9% reduction in major coronary events during the in-trial treatment period (median 4.1 years, P = 0.004), and a further 20% reduction during extended follow-up (median 2.2 years, P < 0.001), for an overall 12% proportional reduction across the full 6.3-year median follow-up, an absolute reduction of 1.8 percentage points. No significant effects emerged on non-vascular mortality, cancer or other serious adverse events. The benefit grew with longer follow-up and no long-term harms emerged, arguing for longer trial and follow-up durations when assessing lipid-modifying drugs.

Original abstract

Aims: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period.

Methods And Results: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants.

Conclusion: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms.

Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

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