Cardiovascular outcomes trial with anacetrapib in subjects with high cardiovascular risk – are major benefits REVEALed?

ABSTRACT

Introduction: The actions of the cholesteryl ester transfer protein (CETP) inhibitors (torcetrapib, dalcetrapib and evacetrapib) include increasing high-density lipoprotein (HDL) cholesterol, but they do not reduce cardiovascular outcomes in subjects with high cardiovascular risk. Anacetrapib also inhibits CETP, increases HDL cholesterol and lowers low-density lipoprotein (LDL) cholesterol.

Areas covered: This evaluation is of the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, which was a cardiovascular outcomes trial with anacetrapib in subjects with high cardiovascular risk. Consideration is given as to whether increasing HDL cholesterol, lowering LDL cholesterol or other mechanisms/factors underlying the positive outcome with this CETP inhibitor.

Expert opinion: After three years, the REVEAL trial with anacetrapib, demonstrated cardiovascular benefits, but not a reduction in coronary artery deaths. The reductions were not significant in years one and two. Thus, in my opinion, the benefits of anacetrapib were not major, and may not apply in ‘real’ world populations where adherence to medicines is lower than in REVEAL. Also, lowering LDL cholesterol and off-target mechanisms of anacetrapib may have contributed to any beneficial and/or toxic effects. Anacetrapib has a good safety profile.

KEYWORDS:

• Anacetrapib
• cholesteryl ester transfer protein (CETP)
• cardiovascular clinical outcomes
• dalcetrapib
• evacetrapib
• HDL cholesterol
• LDL cholesterol
• REVEAL
• torcetrapib

Declaration of interest

S Doggrell has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. One referee is on the scientific advisory board for Merck & Co. while another referee is: an advisor to Merck regarding anacetrapib, a member of the steering committee for DEFINE, an advisor for Eli Lilly and Company regarding evacetrapib and the site principal investigator for the ILLUMINATE trial.

Additional information

Funding

This manuscript has not been funded.