Evacetrapib
Evacetrapib raised HDL-C up to 129% and lowered LDL-C up to 36% alone or with statins in a 398-patient dose-ranging trial (JAMA 2011)
Original title: Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial
This randomized controlled trial tested evacetrapib as monotherapy and combined with statins in 398 patients with elevated LDL-C or low HDL-C. As monotherapy, evacetrapib produced dose-dependent HDL-C increases of 53.6% to 128.8% (30 to 500 mg/d) versus a 3.0% decrease with placebo, and LDL-C decreases of 13.6% to 35.9% versus a 3.9% increase with placebo (P < .001 for all versus placebo). Combined with simvastatin, atorvastatin, or rosuvastatin, evacetrapib 100 mg/d increased HDL-C by 78.5% to 88.5% and decreased LDL-C by 11.2% to 13.9% versus statin monotherapy (P < .001 for all). Compared with evacetrapib alone, adding statins produced greater LDL-C reduction (P < .001) but no additional HDL-C increase (P = .39), and although underpowered for safety, no adverse effects were observed. The authors conclude evacetrapib favorably altered HDL-C and LDL-C alone or with statins, with cardiovascular outcome effects requiring further study.
Original abstract
Context: Interest remains high in cholesteryl ester transfer protein (CETP) inhibitors as cardioprotective agents. Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins.
Objective: To examine the biochemical effects, safety, and tolerability of evacetrapib, as monotherapy and in combination with statins, in patients with dyslipidemia.
Design, Setting, And Participants: Randomized controlled trial conducted among 398 patients with elevated low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels from April 2010 to January 2011 at community and academic centers in the United States and Europe.
Interventions: Following dietary lead-in, 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.
Main Outcome Measures: The co-primary end points were percentage changes from baseline in HDL-C and LDL-C after 12 weeks of treatment.
Results: The mean baseline HDL-C level was 55.1 (SD, 15.3) mg/dL and the mean baseline LDL-C level was 144.3 (SD, 26.6) mg/dL. As monotherapy, evacetrapib produced dose-dependent increases in HDL-C of 30.0 to 66.0 mg/dL (53.6% to 128.8%) compared with a decrease with placebo of -0.7 mg/dL (-3.0%; P < .001 for all compared with placebo) and decreases in LDL-C of -20.5 to -51.4 mg/dL (-13.6% to -35.9%) compared with an increase with placebo of 7.2 mg/dL (3.9%; P < .001 for all compared with placebo). In combination with statin therapy, evacetrapib, 100 mg/d, produced increases in HDL-C of 42.1 to 50.5 mg/dL (78.5% to 88.5%; P < .001 for all compared with statin monotherapy) and decreases in LDL-C of -67.1 to -75.8 mg/dL (-11.2% to -13.9%; P < .001 for all compared with statin monotherapy). Compared with evacetrapib monotherapy, the combination of statins and evacetrapib resulted in greater reductions in LDL-C (P <.001) but no greater increase in HDL-C (P =.39). Although the study was underpowered, no adverse effects were observed.
Conclusions: Compared with placebo or statin monotherapy, evacetrapib as monotherapy or in combination with statins increased HDL-C levels and decreased LDL-C levels. The effects on cardiovascular outcomes require further investigation.
Trial Registration: clinicaltrials.gov Identifier: NCT01105975.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.