Related Experiment Video
Updated: Jan 11, 2026
Bone Marrow Sampling and Transplants
Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL
Stephen J Nicholls1, H Bryan Brewer, John J P Kastelein
1Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland, OH 44195, USA. nichols1@ccf.org
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.
Insights
Evacetrapib effectively raises HDL cholesterol and lowers LDL cholesterol in patients with dyslipidemia, both as a standalone treatment and when combined with statins. Further research is needed to confirm its impact on cardiovascular outcomes.
Area of Science:
- Cardiovascular Pharmacology
- Lipid Metabolism Disorders
Background:
- Cholesteryl ester transfer protein (CETP) inhibitors are investigated for cardioprotective effects.
- Limited data exists on CETP inhibitors combined with statins.
Purpose of the Study:
- To evaluate the biochemical effects, safety, and tolerability of evacetrapib.
- To assess evacetrapib as monotherapy and in combination with statins in dyslipidemic patients.
Main Methods:
- A 12-week randomized controlled trial involving 398 patients with dyslipidemia.
- Participants received placebo, evacetrapib monotherapy (30-500 mg/d), or statin therapy with or without evacetrapib (100 mg/d).
- Primary endpoints were changes in HDL-C and LDL-C levels.
Main Results:
- Evacetrapib monotherapy dose-dependently increased HDL-C and decreased LDL-C compared to placebo.
- Combination therapy with statins significantly increased HDL-C and decreased LDL-C.
- Statin-evacetrapib combination showed greater LDL-C reduction than evacetrapib monotherapy.
Conclusions:
- Evacetrapib, alone or with statins, improves HDL-C and LDL-C levels in dyslipidemic patients.
- The study suggests potential benefits, but cardiovascular outcome effects require further investigation.
