Physicians' Academy for Cardiovascular Education

Larger benefit of CETP inhibitor with longer follow-up

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

Literature - HPS3/TIMI55-REVEAL Collaborative group: Sammons E, Hopewell JC, Chen F et al., - Eur Heart J. 2021, doi: 10.1093/eurheartj/ehab863

The benefit of the CETP inhibitor anacetrapib on major coronary events increases with longer follow-up, shown in a post-trial analysis of patients who had been randomized to anacetrapib compared to those on placebo in the REVEAL trial.

Introduction and methods


The cholesterol ester transfer protein (CETP) inhibitor anacetrapib lowers non-HDL-c, in particular LDL-c. In the HPS3/TIMI55-REVEAL trial, addition of anacetrapib to intensive statin therapy reduced the risk of major coronary events by 9% (95%CI: 3-15%, P=0.004) compared to placebo during a median follow-up of 4.1 years [1.2]. It is slowly eliminated from the circulation because of its accumulation in adipose tissue, which explains lipid-modifying effects years after stopping prolonged treatment [3-5].

In this study, the efficacy and safety are reported of an additional 2 years follow-up following the discontinuation of treatment in the REVEAL study.

Study design

In the REVEAL trial, 30,449 patients ≥50 years with pre-existing ASCVD were randomized to anacetrapib or matching placebo in addition to atorvastatin regimen. After the final follow-up visit, treatment with anacetrapib or placebo and atorvastatin was stopped. In the post-trial follow-up, participants and their doctors remained blinded to the previous randomized treatment. During the post-trial period, information was collected for 26,129 consenting participants by telephone interview or medical record review. Follow-up was a median of 4.1 years for the in -trial period, 2.3 years for the post-trial period and 6.3 years for the combined periods.


The pre-specified outcome for this analysis was the first major coronary event, which was the composite of coronary death, myocardial infarction, or coronary revascularization) during the combined in-trial and post-trial follow-up period.

Main results

First major coronary event

Secondary CV outcomes

Recurrent vascular events

Mortality, cancer and other serious adverse events


Long-term follow-up of patients in the REVEAL trial showed that patients who had been randomized to anacetrapib had reduced risk of major coronary events compared to patients who had been randomized to placebo. No safety signals emerged with longer follow-up.

The authors conclude that these results emphasize the importance of sufficiently long treatment and follow-up in randomized trials of lipid-modifying medication in order to full assess benefits and potential harms.


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Find this article online at Eur Heart J

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