Anacetrapib Reduced Risk of Cardiovascular Events

Despite early reports that questioned the future of anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, the drug appears to be on its way to success, showing more benefit than risk in its trial results.

In a study randomizing 30449 patients, anacetrapib resulted in a 9% reduction in the risk of a major coronary event (P­=0.004). After a follow-up of 4.1 years, patients receiving anacetrapib experienced these events at a rate of 10.8%, compared to 11.8% in the placebo group.

The results of the Randomized Evaluation of the Effects of Anacetrapib through Lipid-modification (REVEAL) trial were presented at the European Society of Cardiology (ESC) Congress in Barcelona.

“The REVEAL trial has shown for the first time that adding anacetrapib to intensive statin therapy reduces the incidence of cardiovascular events in high-risk patients,” Martin Landray (pictured), PhD, the co-principal investigator, and professor of medicine and epidemiology at Oxford University, said in a statement. “The scale of reduction was similar to other LDL cholesterol lowering drugs, such as statins. The large increase in HDL cholesterol levels produced by anacetrapib did not appear to have much impact on risk.”

The participants were treated with atorvastatin to ensure LDL control and then were randomly assigned 100 mg of daily anacetrapib or placebo for an average of 4 years. The results showed that adding the drug to statin therapy reduced LDL levels by 20% while doubling the HDL cholesterol levels.

There were no major concerns about safety, and no increase in death, cancer, or serious medical events, however a small increase in blood pressure and a small reduction in kidney function was shown.

“These findings are in marked contrast to the disappointing results of previous trials of other CETP inhibitors which were stopped after about two years due to unexpected hazards or an apparent lack of efficacy,” Landray added.

Investigators found, in subsidiary analyses, that the drug significantly reduced the composite outcome of coronary death or myocardial infarction, as well as coronary revascularization. There was also a slight reduction in the risk of diabetes when the drug was coupled with statin therapy.

“The REVEAL trial recruited around twice as many participants as any other trial of a CETP inhibitor collected information on double the number of cardiovascular events, and gave CETP treatment for twice as long,” Louise Bowman, MD, co-principal investigator, associate professor of clinical trials and epidemiology at Oxford, said. “The full effects of anacetrapib did not appear until after the first year. A similar pattern has been observed in randomized trials of statin therapy. Consequently, previous trials of CETP inhibitors may have been too short for any benefits to emerge.”

The drug's future is still uncertain, as it appears that Merck, the company producing it, has not made a public statement about a desire to move forward.

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