medwireNews: Adding obicetrapib, a selective cholesteryl ester transfer protein inhibitor, to existing lipid-lowering therapy reduces low-density lipoprotein (LDL) cholesterol levels by 30% in patients with atherosclerotic cardiovascular (CV) disease or heterozygous familial hypercholesterolemia at high risk for CV events, shows the BROADWAY study.
The study was published in The New England Journal of Medicine and simultaneously presented at the European Atherosclerosis Society Annual Congress 2025, held in Glasgow, UK.
A total of 2530 patients deemed at high risk for CV events despite receiving maximum tolerated doses of statins with or without other lipid-lowering therapies were included.
High CV risk was denoted by serum LDL cholesterol levels of at least 100 mg/dL (2.59 mmol/L) or non-high-density lipoprotein (non-HDL) cholesterol levels of 130 mg/dL (3.37 mmol/L). Patients with LDL cholesterol levels of 55–100 mg/dL (1.42–2.59 mmol/L) or non-HDL levels of 85–130 mg/dL (2.20–3.37 mmol/L) were also considered if they had at least one CV risk factor such as a myocardial infarction within the preceding 3 to 12 months, type 2 diabetes, or were a current smoker or older than 60 years of age.
The participants were a mean of 65 years old, 66% were men, the mean BMI at baseline was 29 kg/m², and the mean LDL cholesterol level was 84 mg/dL (2.17 mmol/L). In all, 89% had atherosclerotic CV disease, and 17% had heterozygous familial hypercholesterolemia. Around 90% were on statin therapy, 70% of whom were receiving high-intensity statins.
The 1686 participants were randomly assigned to receive 365 days of adjunct oral obicetrapib 10 mg, while 844 received matched placebo. At day 84, the least squares mean reduction in LDL cholesterol was 29.9% with obicetrapib versus an increase of 2.7% with placebo, translating to a significant 32.6 percentage point greater reduction with obicetrapib.
The obicetrapib- and placebo-treated patients achieved mean LDL cholesterol levels at day 84 of 62.8 mg/dL (1.62 mmol/L) versus 92.3 mg/dL (2.39 mmol/L). Additionally, at this timepoint, 27.9% of the obicetrapib group had LDL cholesterol levels below 40 mg/dL (1.03 mmol/L) and 51.0% had levels below 55 mg/dL (1.42 mmol/L), compared with only 1.1% and 8.0% of the placebo group, respectively.
Obicetrapib treatment also resulted in greater improvements in apolipoprotein B, non-HDL cholesterol, triglycerides, HDL cholesterol, and apolipoprotein A1 compared with placebo, with corresponding between group differences of −18.9, −29.4, −7.8, +136.3, and +43.2 percentage points.
“These findings suggest that obicetrapib may be a useful adjunct to lipid lowering in patients at high risk for [CV] events,” say researchers Stephen Nicholls (Monash University, Clayton, Victoria, Australia) and colleagues, although they add that “the efficacy and safety of longer-term administration require further investigation.”
The investigators highlight that “treatment goals [for LDL cholesterol] are not reached in many high-risk patients, despite the use of maximum tolerated doses of statins,” therefore more effective lipid-lowering approaches, such as combination therapies, are increasingly needed.
They say that “[f]urther clinical studies are needed to determine whether [obicetrapib] will be a useful therapy for the prevention of atherosclerotic cardiovascular disease.”
Adverse events occurred in 59.7% of patients in the obicetrapic group and 60.8% of those in the placebo group. The most common adverse events were hypertension (4.9 vs 3.9%) and upper respiratory tract infection (2.9 vs 3.9%). There were 19 deaths from any cause in the obicetrapib group and 12 in the placebo group, of which a respective five and four were due to coronary heart disease.
The researchers say that, regarding adverse events, “no apparent differences were observed between the groups with respect to severity, relationship to the trial regimen, or the rationale for stopping treatment.”
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N Engl J Med 2025; doi:10.1056/NEJMoa2415820
EAS Congress 2025; Glasgow, UK: 4-7 May
