REVEAL Anacetrapib CETP inhibitor results revealed this morning. We already knew they hit their topline target. But the full data revealed this morning at ESC isn't too impressive. In a trial with more than 30,000 patients treated for a bit over 4 years on average, the study investigators observed a 9% relative risk reduction in the cardiovascular events defined in their primary outcome (10.8% compared to 11.8%). But hey, they got a p-value of 0.004 if that makes them feel better! Just to put this in perspective, the trial population that BETonMACE is modeled after is similar to that of the EXAMINE trial who experienced an ~11% event rate at 18 months of follow up (relative to ~11% at 4 years of follow up in REVEAL). 

However, the primary outcome in REVEAL was the occurrence of a major coronary event, including heart attack, coronary revascularisation (coronary stenting or bypass surgery), or death from heart disease. The investigators concluded that the drug missed the key secondary endpoint of their composite of major atherosclerotic events: myocardial infarction, coronary death or presumed ischemic stroke, which is the "gold standard" 3-point MACE that many more recent cardiovascular outcomes trials are based on including BETonMACE.

From the ESC press release "In subsidiary analyses, anacetrapib significantly reduced the composite outcome of coronary death or myocardial infarction as well as coronary revascularisation. There was no significant effect on ischaemic stroke." So it sounds like coronary death and MI were reduced, but not stroke.

Also interesting, as stated in the ESC release, "Adding anacetrapib to statin therapy reduced LDL cholesterol levels by at least 20% and doubled the level of HDL cholesterol."  So much, if not all, of the MACE reducing effect of anacetrapib may be due to LDL-lowering. Also, this drug accumulates in fat tissue and hangs around in the body for up to 5 years. Very unlikely this drug ever makes it to market in my opinion.

"Merck hits a bloop single in an epic PhIII CETP cardio contest. Now what?" by EndPoint News' John Carroll

"Anacetrapib reduces risk of serious cardiovascular events in high risk patients on statins (REVEAL)" ESC news release

"Anacetrapib REVEALs 'Modest' Effect on Cardiovascular Outcomes" Sue Hughes Medscape article.