Evacetrapib in Dyslipidemia Patients

Evacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, increased high-density lipoprotein cholesterol (HDL-C) levels and decreased low-density lipoprotein cholesterol (LDL-C) levels in patients with dyslipidemia as monotherapy or in combination with statins when compared with placebo or statin therapy alone, according to the findings of a new randomized controlled trial. The results of the multicenter study were recently published in the Journal of the American Medical Association [2011;306(19):2099-2109]. Although statins have been shown to reduce LDL-C, cardiovascular disease is still the leading cause of death, and researchers continue to look for additional therapy options. CETP inhibitors have been investigated as 1 therapy option; however, limited research has been done to investigate the combined effect of statin therapy and CETP inhibitors. In this double-blind study, researchers assessed the biochemical efficacy, safety, and tolerability of evacetrapib when used as monotherapy or in combination with statin medications for a 12-week period. Researchers established a multicenter trial where 398 patients were randomized to either receive a placebo; evacetrapib monotherapy with 1 of 3 dose options (30, 100, or 500 mg/day); or statin therapy with 1 of 3 statin options (40 mg/day of simvastatin, 20 mg/day of atorvastatin, or 10 mg/day of rosuvastatin) that were given alone or in combination with 100 mg/day of evacetrapib. All patients participated in a 2- to 8-week dietary lead-in period. To be included in the trial, patients had to be at least 18 years of age and meet either the low HDL-C criteria or the high LDL-C criteria established by researchers. The low HDL-C criteria were defined as an HDL-C level of <45 mg/dL for men or 50 mg/dL for women along with an LDL-C level that met the National Cholesterol Education Program Adult Treatment Panel III goal. Patients who met the high LDL-C criteria were described as those patients who either (1) had an LDL-C level between 100 and 190 mg/dL with 0 or 1 risk factors; (2) an LDL-C level between 100 and 130 mg/dL with at least 2 risk factors and a 10-year coronary risk of <10%; or (3) an LDL-C level between 100 and 130 mg/dL with at least 2 risk factors and a 10-year coronary risk between 10% and 20%. The coprimary end points of the trial were the percentage change from baseline in HDL-C and LDL-C after the 12-week treatment period. Based on the results of the study, researchers found that evacetrapib increased HDL-C levels and decreased LDL-C levels when used alone or in combination with statins. They found that evacetrapib monotherapy resulted in dose-dependent HDL-C increases that ranged from 30.0 to 66.0 mg/dL (53.6%-128.8%; P<.001 compared with a placebo) and LDL-C decreases that ranged from −20.5 to −51.4 mg/dL (−13.6% to −35.9%; P<.001 compared with placebo). When used in combination with statins, evacetrapib increased HDL-C levels by 42.1 to 50.5 mg/dL (78.5%-88.5%; P<.001 for all compared with statin alone) and resulted in decreases in LDL-C of −67.2 to −75.8 mg/dL (−11.2% to −13.9%; P<.001 for all compared with statin alone). When researchers compared evacetrapib monotherapy with the combined therapy, they found that the combination of statins and evacetrapib produced greater decreases in LDL-C (P<.001) than evacetrapib monotherapy; however, there was no greater increase in HDL-C (P=.39). Researchers also assessed the safety of evacetrapib and reported no increase in blood pressure for patients taking evacetrapib compared with the placebo group. In addition, they found no difference between the control groups and those taking evacetrapib in either the monotherapy or combination setting in adverse events.