New medication increases HDL cholesterol and decreases LDL cholesterol levels

Among patients with sub-optimal low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) levels, use of the drug evacetrapib alone or in combination with statin medications was associated with significant increases in HDL-C levels and decreases in LDL-C levels, according to a study appearing in the November 16 issue of JAMA, a theme issue on cardiovascular disease. The study is being released early online to coincide with its presentation at the American Heart Association Scientific Sessions.

Cardiovascular disease remains the leading cause of death. "Accordingly, considerable efforts have focused on development of novel therapeutic agents designed to address residual cardiovascular risk. Because individuals from the general population with elevations of HDL-C have a reduced incidence of coronary heart disease, it has been assumed that finding an appropriate therapy to increase HDL-C levels would yield substantial clinical benefit. However, development of drugs that increase HDL-C levels has been challenging and fraught with failures, including the premature termination of a large outcomes trial studying the effects of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib. Despite failure of the first drug in the class, considerable interest remains in CETP inhibition as a therapeutic strategy, by virtue of the ability of these agents to substantially increase HDL-C levels and, in some cases, reduce LDL-C levels," according to background information in the article. "Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins."

Stephen J. Nicholls, M.B.B.S., Ph.D., of the Cleveland Clinic, and colleagues evaluated the biochemical efficacy, safety, and tolerability of the CETP inhibitor evacetrapib as monotherapy and in combination with statin agents commonly used in clinical practice in patients with dyslipidemia. The randomized controlled trial, which included 398 patients with elevated LDL-C or low HDL-C levels, was conducted from April 2010 to January 2011 at community and academic centers in the United States and Europe. Patients were randomly assigned to receive placebo (n=38); evacetrapib monotherapy, 30 mg/d (n=40), 100 mg/d (n=39), or 500 mg/d (n=42); or statin therapy (n=239) (simvastatin, 40 mg/d; atorvastatin, 20 mg/d; or rosuvastatin, 10 mg/d) with or without evacetrapib, 100 mg/d, for 12 weeks. The primary outcomes measured were percentage changes in HDL-C and LDL-C levels at the beginning of the trial to after 12 weeks of treatment. The average age of the participants was 58 years, and 56 percent were women.

The average lipid levels at the beginning of the study were 55.1 mg/dL for HDL-C and 144.3 mg/dL for LDL-C. The researchers found that as monotherapy, evacetrapib produced dose-dependent increases in HDL-C of 30.0 to 66.0 mg/dL (53.6 percent to 128.8 percent) compared with a decrease with placebo of -0.7 mg/dL (-3.0 percent) and decreases in LDL-C of -20.5 to -51.4 mg/dL (-13.6 percent to -35.9 percent) compared with an increase with placebo of 7.2 mg/dL (3.9 percent). The HDL-C changes were significantly greater among patients with lower levels of HDL-C or higher triglyceride levels at baseline.