CETP inhibition
Evacetrapib cuts Lp(a) by up to 40% alone and small LDL particles by up to 95%, a randomised trial of 393 patients (J Clin Lipidol 2016)
Original title: Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients
This placebo-controlled trial measured VLDL and LDL particle concentrations and Lp(a) at baseline and week 12 in 393 mildly hypercholesterolaemic patients treated with the CETP inhibitor evacetrapib alone (30, 100, or 500 mg/day) or combined with a statin (simvastatin, atorvastatin, or rosuvastatin). Evacetrapib monotherapy produced dose-dependent reductions in Lp(a) (up to -40% at 500 mg), total LDL particle concentration (up to -54%), and small LDL particle concentration (up to -95%). Combined with statins, evacetrapib further reduced Lp(a) (-31%), LDL particle concentration (-22%), and small LDL particles (-60%) compared with statin alone, while the proportion of patients above optimal LDL particle and small LDL particle thresholds fell from 88% and 55% at baseline to 20% and 12% at week 12 with combination therapy. Evacetrapib also significantly increased LDL particle size. The findings show evacetrapib, alone or with statins, significantly reduces atherogenic apoB-containing lipoproteins including Lp(a).
Original abstract
Background: Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk.
Objectives: To evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients.
Methods: VLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30 mg/d, 100 mg/d, or 500 mg/d) or in combination with statins (100 mg plus simvastatin 40 mg/d, atorvastatin 20 mg/d, or rosuvastatin 10 mg/d; Clinicaltrials.gov Identifier: NCT01105975).
Results: Evacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to -40% with evacetrapib 500 mg), total LDL particle (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (-31%), LDL-P (-22%), and sLDL (-60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000 nmol/L) and sLDL (>600 nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size.
Conclusions: Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.