Patients receiving the cholesteryl ester transfer protein inhibitor obicetrapib experienced a notable reduction in coronary events after 6 months of treatment compared with placebo, according to a recent study.

In a pooled analysis published in JACC, researchers examined the effects of obicetrapib on major adverse cardiovascular events (MACE) in high-risk patients. The analysis combined data from both the phase III randomized, double-blind BROADWAY and BROOKLYN trials, which involved 2,884 adults with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia. The participants (mean age = 66 years; 36% women) were randomly assigned in a 2:1 ratio to receive 10 mg of obicetrapib or placebo daily for 12 months while continuing maximally tolerated lipid-lowering therapy. The trials primarily evaluated lipid changes, with MACE assessed post hoc by blinded adjudication.

At baseline, the patients had a median of 92 mg/dL for low-density lipoprotein cholesterol (LDL-C), 88 mg/dL for apolipoprotein B (ApoB), 116 mg/dL for non–high-density lipoprotein cholesterol (non-HDL-C), and 40.5 nmol/L for lipoprotein(a) [Lp(a)]. Compared with placebo, obicetrapib produced greater respective absolute and percentage reductions in LDL-C (−34.0 vs −4.0 mg/dL, −37.8% vs −4.6%), ApoB (−19.0 vs −3.0 mg/dL, −21.7% vs −3.6%), non-HDL-C (−36.0 vs −4.0 mg/dL, −32.4% vs −3.7%), and Lp(a) (−9.8 vs 0 nmol/L, −32.5% vs 0%). Treatment with obicetrapib also increased HDL-C, with absolute and percentage changes of  +68.0 vs +1.0 mg/dL and +140.0% vs +1.5%).

During the 12-month follow-up, 123 patients (4.3%) experienced at least one cardiovascular event. The four-component MACE occurred in 3.9% of patients treated with obicetrapib compared with 5.0% of those who received placebo, corresponding to a hazard ratio (HR) of 0.77. The three-component MACE occurred in 3.2% and 4.7% of patients, respectively (HR = 0.68). When analyzed by time, the benefit of obicetrapib emerged after 6 months of treatment, with the HR decreasing to 0.60 for the four-component and 0.45 for the three-component MACE beyond.

“These observations encourage a reconsideration of the lipid focus of [cholesteryl ester transfer protein] inhibition from HDL-C raising to lowering of atherogenic lipid and lipoprotein parameters,” noted lead study author Stephen J. Nicholls, MBBS, PhD, of the Victorian Heart Institute at Monash University in Australia, and colleagues.

Analyses of achieved lipid levels showed that lower LDL-C, ApoB, non-HDL-C, and Lp(a) concentrations were associated with fewer cardiovascular events, whereas higher HDL-C levels were linked to lower risk.

The BROOKLYN and BROADWAY trials were funded by NewAmsterdam Pharma. Several investigators, including Dr. Nicholls; Adam J. Nelson, MBBS, PhD; Kausik K. Ray, MD, MPhil, FMedSci; Christie M. Ballantyne, MD; Michael Szarek, PhD; Andrew Hsieh, PharmD; John J. Kastelein, MD, PhD; and Michael H. Davidson, MD, reported research support, consulting roles, or employment relationships with pharmaceutical companies, as detailed in the publication.

Source: JACC