This research is presented as a late-breaking clinical trial at the American Heart Association Scientific Sessions and published simultaneously in the New England Journal of Medicine on November 17, 2010.
“There are very few drugs available to treat low levels of good cholesterol, and this new drug, anacetrapib, is four to ten times more effective in raising good cholesterol compared to current therapies,” said Christopher Cannon, MD, a cardiologist and senior investigator in the TIMI Study Group in the Cardiovascular Division at BWH and lead author of the DEFINE trial (Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib). “Our research shows that anacetrapib is well tolerated by patients and is not associated with the dangerous blood pressure changes that have been seen in similar types of medication. If these same findings are validated in larger scale trials than we may have a new kind of drug to fight cardiovascular disease.”
The new drug, anacetrapib, belongs to a new class of drugs called cholesteryl ester transfer protein inhibitors or CETPs, which block the transfer of triglycerides and esters between good and bad cholesterol. Previous research has shown that high levels of HDL (good) cholesterol protect against heart attack. While experts are unsure of exactly why this protection occurs, they suspect that HDL is responsible for carrying bad cholesterol away from the arteries and out of the body.
In a randomized, double-blind, placebo-controlled trial, the gold standard for research studies, Cannon and colleagues enrolled 1623 participants who were taking a statin to treat coronary heart disease (CHD) or cardiovascular risk factors equivalent to CHD. Participants were randomized to receive either 100 mg of anacetrapib or placebo for 18 months.
Researchers found a 138 percent boost in HDL among the patients taking anacetrapib (from 40 to 101 mg/dl versus 40 to 46 mg/dl in the placebo group). There are no currently available therapies that increase HDL so dramatically. In addition, patients who were treated with anacetrapib experienced a 40 percent reduction in LDL (81 to 45 mg/dl versus 82 to 77 mg/dl for placebo). No significant issues were observed between the two groups in safety measures, such as changes in blood pressure.
The study also evaluated adverse effects on cardiovascular events and researchers observed a trend toward fewer cardiovascular safety events, providing 94 percent confidence that anacetrapib did not have the same adverse effect that was seen with the previously studied CETP agent, torcetrapib. Interestingly, there was a significantly lower rate of the need for angioplasty or bypass surgery for patients in the anacetrapib group, and overall there were fewer total cardiovascular events compared to the placebo group.
“Especially important to note is that even though all the participants in the study were taking another cholesterol-lowering drug, adding anacetrapib was what allowed them to reach previously unattainable levels of good and bad cholesterol,” Cannon said. “We look forward to larger studies of anacetrapib, and are excited about the potential for a new class of drugs to treat those patients with an increased risk for heart attack and stroke due to arthrosclerosis.”
The DEFINE study and the study analyses were funded by Merck Research Laboratories, which also manufactures anacetrapib.