November 17th, 2010
Anacetrapib: “Knock-Your-Socks-Off Effect on HDL and a Jaw-Dropping Effect on LDL”
Following the failure of torcetrapib in 2006, the future of cholesteryl ester transfer protein (CETP) inhibitors appeared quite troubled. Now, with the results of DEFINE (Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib), presented at the AHA in Chicago and published online in the New England Journal of Medicine, the future for this novel class of drugs appears much brighter, but the final decision about anacetrapib will have to wait for a larger clinical trial.
DEFINE was designed to assess the side-effect and overall safety profile of anacetrapib, as well as its effects on lipids. The trial randomized 1623 patients already taking statins or other lipid-lowering agents to either anacetrapib or placebo for 18 months.
The primary endpoints of the study were the percent change in LDL at 24 weeks and the side-effect profile at 76 weeks. Compared to its effect on placebo, anacetrapib reduced LDL by 40% and raised HDL by 138%:
LDL at baseline and 24 weeks:
- Anacetrapib: 81 mg/dL and 45 mg/dL
- Placebo: 82 mg/dL and 77 mg/dL
HDL at baseline and 24 weeks:
- Anacetrapib: 41 mg/dL and 101 mg/dL
- Placebo: 40 mg/dL and 46 mg/dL
There were no differences between the groups in blood pressure, electrolytes, or aldosterone levels associated with anacetrapib.
There were 16 (2%) adjudicated cardiovascular events in the anacetrapib group versus 21 (2.6%) events in the placebo group. There were 8 revascularizations with anacetrapib versus 28 with placebo.
“Anacetrapib has a knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL,” said Chris Cannon, the study’s first author, in an AHA press release.