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17-11-2011 | Cardiometabolic | Article

Evacetrapib raises HDL, lowers LDL cholesterol

Abstract

JAMA

2011: Advance online publication

MedWire News: Treatment with evacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, administered as monotherapy or in combination with statins, increases high-density lipoprotein (HDL) cholesterol levels and decreases low-density lipoprotein (LDL) cholesterol levels after 12 weeks, US researchers report.

"The results of the current study provide the foundation for a large Phase III clinical trial designed to assess the efficacy and safety of evacetrapib," said lead author Stephen Nicholls (Cleveland Clinic, Ohio, USA) speaking at the 2011 American Heart Association Scientific Sessions in Orlando, Florida, USA.

The study involved 393 patients (mean age 58.3 years) with elevated LDL cholesterol or low HDL cholesterol levels at baseline, who were recruited between April 2010 and January 2011.

Following an 8-week dietary run-in period and withdrawal of lipid-modifying therapies, patients were randomly assigned to one of 10 treatment groups: placebo (n=38); evacetrapib monotherapy, 30 mg/day (n=40), 100 mg/day (n=39), or 500 mg/day (n=42); or statin therapy (simvastatin40 mg/day, atorvastatin 20 mg/day, or rosuvastatin 10 mg/day) with or without evacetrapib at 100 mg/day (n=239).

At baseline, mean LDL and HDL cholesterol levels were 144.3 mg/dL and 55.1 mg/dL, respectively. After 12 weeks of treatment, a dose-dependent increase in HDL cholesterol levels was observed with evacetrapib monotherapy, ranging from 53.6% to 128.8%, compared with placebo. Similarly, a dose-dependent reduction in LDL cholesterol was observed, ranging from 13.6% to 35.9%.

Additionally, administration of evacetrapib 100 mg in combination with statins resulted in a similar degree of elevation of HDL cholesterol and a reduction in LDL cholesterol, commented Nicholls. Specifically, when compared with statin monotherapy, increases in HDL cholesterol levels ranging from 78.5% to 88.5% and reductions in LDL cholesterol levels ranging from 11.2% to 13.9% were observed.

The combination of statins and evacetrapib resulted in significantly greater reductions in LDL cholesterol when compared with evacetrapib monotherapy, but there was no greater increase in HDL cholesterol, the authors noted.

Discussing the results, Daniel Rader (University of Pennsylvania, PA, USA) said that there is "overwhelming evidence" that reducing LDL cholesterol and other atherogenic apolipoprotein B-containing lipoproteins reduces cardiovascular risk. However, he said, "we continue to have questions about the so-called HDL cholesterol hypothesis. The new class of CETP inhibitors has the potential to definitively address this very important hypothesis."

He concluded: "The real importance here is that another apparently safe CETP inhibitor is entering into what we hope will be clinical outcome trials, affording the opportunity to test some additional key questions that are not being fully addressed with the current CETP inhibitors."

The final study report is published in the Journal of the American Medical Association.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Nikki Withers