June 21, 2025

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Long Term Use Of Anacetrapib Reduces Major Coronary Events

Studies have shown that inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces low-density lipoprotein (LDL) cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. In a recent study, researchers have reported that beneficial effects of anacetrapib on major coronary events increased with longer follow-up and no adverse event.
The study findings were published in the European Heart Journal on December 15, 2021.
HPS3/TIMI55-REVEAL was the first randomized controlled trial to demonstrate that adding CETP inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. Dr E Sammons and his team previously reported that adding anacetrapib to intensive statin therapy for a median of 4 years reduced the incidence of major coronary events. Recently they conducted an extended follow-up beyond the scheduled study treatment period of the REVEAL study.
The REVEAL study includes 30, 449 adults with prior atherosclerotic vascular disease who were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, the researchers enrolled 26 129 survivors in a post-trial follow-up period, blind to their original treatment allocation. The major outcome was the 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.
Key findings of the study:
The researchers noted that allocation to anacetrapib conferred a 9% 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), they found that there was a further 20% reduction.
Overall, they observed a 12% proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% absolute reduction.
They reported no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events.
The authors concluded, "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."
For further information:
DOI: https://doi.org/10.1093/eurheartj/ehab863

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