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

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• The REVEAL trial initially demonstrated that adding cholesteryl ester transfer protein (CETP) inhibitor therapy to statins reduced major coronary events.
• Extended follow-up data are crucial for fully assessing the long-term efficacy and safety of lipid-modifying agents.

Purpose of the Study:

• To report the results of extended follow-up from the REVEAL trial, assessing the long-term impact of anacetrapib on major coronary events.
• To evaluate the safety profile of anacetrapib beyond the initial study treatment period.

Main Methods:

• 30,449 adults with atherosclerotic vascular disease were randomized to anacetrapib or placebo, alongside atorvastatin.
• Participants entered a post-trial follow-up period, blinded to treatment allocation, after the scheduled treatment ended.
• The primary outcome was major coronary events (coronary death, myocardial infarction, revascularization) analyzed by intention-to-treat.

Main Results:

• Anacetrapib conferred a 9% reduction in major coronary events during the treatment period (median 4.1 years).
• During extended follow-up (median 2.2 years), anacetrapib showed a further 20% reduction in major coronary events.
• Overall, anacetrapib resulted in a 12% proportional reduction in major coronary events over a median of 6.3 years, with no significant adverse effects on non-vascular mortality or cancer.

Conclusions:

• The cardiovascular benefits of anacetrapib increased with longer follow-up duration.
• No new safety concerns, including non-vascular mortality or cancer, emerged during the extended follow-up.
• Sufficiently long treatment and follow-up are essential for comprehensive evaluation of lipid-modifying therapies.