Evacetrapib
ACCENTUATE: evacetrapib beat ezetimibe and higher-dose statin on LDL-C and Lp(a), but also raised hsCRP, a clue to why ACCELERATE later failed (Atherosclerosis 2017)
Original title: Comparative effects of cholesteryl ester transfer protein inhibition, statin or ezetimibe on lipid factors: The ACCENTUATE trial
The ACCENTUATE trial randomised 366 patients with atherosclerotic cardiovascular disease or diabetes, stabilised on atorvastatin 40 mg, to atorvastatin plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin plus ezetimibe 10 mg, or atorvastatin plus placebo for 90 days at 64 US centres. Evacetrapib reduced LDL-C by 33%, more than ezetimibe (27%), higher-dose statin (6%) or statin alone (0%), cut apoB by 23% versus 19% and 7%, and reduced Lp(a) by 29% versus all other groups. Evacetrapib also raised HDL-C by 125%, apoA-I by 46%, apoC-III by 50% and apoE by 28%, and increased non-ABCA1-mediated efflux by 53% and ABCA1-mediated efflux by 13% versus comparators. However, evacetrapib raised hsCRP compared with ezetimibe. While evacetrapib improved traditional and putative protective lipid measures more than the comparators, it also adversely affected novel atherogenic risk markers, findings that may help explain the subsequent lack of clinical benefit in the ACCELERATE outcomes trial.
Original abstract
Background And Aims: The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters.
Methods: 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States. Lipid parameters, safety and tolerability were measured.
Results: Addition of evacetrapib significantly reduced LDL-C (-33%) compared with ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%, p<0.001). Evacetrapib also decreased apoB by 23% compared to 19% with ezetimibe (p=0.06) and 7% with increased statin dose (p<0.001), and reduced Lp(a) by 29% (p<0.001 vs. other groups). Evacetrapib increased HDL-C (+125%), apoA-I (+46%), apoC-III (+50%) and apoE (+28%) (p<0.001 vs. other groups). Non-ABCA1-mediated efflux increased by 53% (p<0.001 vs. other groups) with evacetrapib. ABCA1-mediated efflux also increased by 13% with evacetrapib (p<0.001 vs. ezetimibe, p=0.002 vs. increasing statin dose, and p=0.004 vs. statin alone). Addition of evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe (p=0.02).
Conclusions: While evacetrapib improved traditional atherogenic and putative protective lipid measures compared with ezetimibe and increasing statin dose in patients with ASCVD and/or diabetes, it also adversely affected novel atherogenic risk factors. These findings may contribute to the lack of clinical benefit observed in the ACCELERATE trial.
evacetrapibmechanismsoutcomes trials
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.