Cholesterol Drug Fails to Reduce Major Cardiovascular Events

A cholesterol drug does not reduce the rates of major adverse cardiovascular events, according to research presented at the American College of Cardiology's 65th Annual Scientific Session.

The investigational drug evacetrapib has the ability to lower low-density lipoprotein (LDL) and increase levels of high-density lipoprotein (HDL). However, the drug was discontinued early in a clinical trial because of other poor results.

“Here we've got an agent that more than doubles the levels of good cholesterol and lowers bad cholesterol and yet has no effect on clinical events,” said lead study author Stephen Nicholls, MBBS, PhD. “We were disappointed and surprised by the results.”

Researchers conducted a phase 3 randomized, double-blind trial with more than 12,000 patients at high risk for serious cardiovascular problems who were administered evacetrapib. About 540 global health centers were included in the study.

For at least 18 months, participants were randomized to receive either 130 milligrams of evacetrapib or a placebo daily. Each patient received standard medical therapy during the trial, with most cases treated with statins or other cholesterol lowering drugs.

All participants had either acute coronary syndrome, cerebrovascular atherosclerotic disease, or both diabetes and coronary artery disease.

“We tested the drug in high-risk patients because they are the patients with the greatest need for new drugs above and beyond what we already use in our clinics,” Nicholls said. “Low risk patients could be another group of patients that could potentially benefit from this drug, but we didn't test that and to do so would require an extraordinarily large study that asks a different question from the one our study was designed to address.”

The results of the study showed that patients in the evacetrapib group had a 37% decrease in LDL cholesterol, while their HDL cholesterol increased by 130% compared with the placebo group.

Evacetrapib was not found to have any major side effects or safety concerns. Additionally, no difference was found between the groups in the study’s primary endpoint.

Evacetrapib is the third failure in the cholesteryl ester transfer protein (CETP) inhibitor drug class. CETPs are designed to disrupt the natural process of HDL cholesterol concerting into LDL cholesterol within the body.

During a phase 3 clinical trial, the first CETP inhibitor drug torcetrapib was abandoned because it was found to increase the risk of cardiovascular events and death. Additionally, the development of the second drug, dalcetrapib, was stopped during a phase 2 clinical trial because it was found to be ineffective.

“There has been, and continues to be, a lot of confusion about what's going on with this class of drugs, since we don't yet have one that can be brought to the clinic to prevent heart attack and stroke in our patients,” Nicholls said. “As we close out the trial, we're trying to understand how a drug that seems to do all the right things in terms of blood cholesterol levels doesn't then translate into reducing clinical events.”