Physicians' Academy for Cardiovascular Education

Combination of CETP inhibitor plus ezetimibe reduces LDL-c in dyslipidemia patients on high-dose statins

Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: A randomized phase 2 trial

Literature - Ballantyne CM, Ditmarsch M, Kastelein JJP, et al. - J Clin Lipidol. 2023 May 31;S1933-2874(23)00186-1 [Online ahead of print]. doi: 10.1016/j.jacl.2023.05.098

Introduction and methods


Among high-risk patients with ASCVD, use of high-intensity statin therapy is suboptimal and only few receive combination lipid-lowering therapy, resulting in frequent failure to achieve guideline-mandated LDL-c treatment goals [1-3]. Increasing evidence suggests that additional lipid-lowering agents, in combination with intensive statin therapy, are required to achieve low LDL-c levels [4,5].

Early studies have shown that obicetrapib, an oral, selective cholesteryl ester transfer protein (CETP ) inhibitor, reduced LDL-c levels by up to 50% and was well tolerated when administered to patients with dyslipidemia as monotherapy in combination with moderate- or high-intensity statins [6,7].

Aim of the study

The study aim was to evaluate the lipid-altering efficacy and safety of combination therapy with obicetrapib and ezetimibe in patients with suboptimally controlled LDL-c levels despite high-intensity statin therapy.


The ROSE2 trial (Study to Evaluate the Effect of Obicetrapib in Combination with Ezetimibe as an Adjunct to High Intensity Statin Therapy) was a multicenter, placebo-controlled, double-blind, phase 2 RCT conducted in the US. Patients with LDL-c >70 mg/dL and triglycerides (TG) <400 mg/dL on stable high-intensity statin therapy (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) were randomized to the combination of obicetrapib 10 mg plus ezetimibe 10 mg (n=40), obicetrapib 10 mg only (n=39), or placebo (n=40) for 12 weeks. Exclusion criteria were, among others, clinically manifest ASCVD.


The primary endpoint was the percent change (from baseline to week 12) in Friedewald-calculated LDL-c level for the obicetrapib plus ezetimibe combination treatment group compared with placebo. Secondary efficacy endpoints included percent changes (from baseline to week 12) in LDL-c level for obicetrapib monotherapy versus placebo and in apoB for obicetrapib plus ezetimibe combination versus placebo and obicetrapib monotherapy versus placebo groups.

Exploratory efficacy endpoints included percent changes (from baseline to week 12) in other lipids, lipoprotein particles, PCSK9, and the proportion of participants that achieved LDL-c<100, <70, and <55 mg/dL at the end of treatment for obicetrapib combination therapy and monotherapy groups compared with placebo.

Safety and tolerability were also assessed.

Main results




The ROSE2 trial showed that combination treatment with obicetrapib and ezetimibe for 12 weeks, as an adjunct to high-intensity statin therapy, reduced the median LDL-c level by 63% in patients with LDL-c >70 mg/dL and TG <400 mg/dL, compared with 44% for obicetrapib monotherapy and 6% for placebo. Both obicetrapib combination therapy and monotherapy also decreased levels of apoB, non–HDL-c, and total and small LDL particles compared with placebo. The combination of obicetrapib plus ezetimibe significantly was safe and well tolerated.


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Find this article online at J Clin Lipidol.

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