SAFETY AND EFFICACY OF OBICETRAPIB IN PATIENTS AT HIGH CARDIOVASCULAR RISK

IF 5.9 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

American journal of preventive cardiology Pub Date : 2025-09-01 DOI:10.1016/j.ajpc.2025.101133

Andrew Hsieh PharmD , Stephen J Nicholls MBBS PhD , Adam J Nelson MBBS, PhD , Marc Ditmarsch MD , John JP Kastelein MD, PhD , Christie M Ballantyne MD , Kausik K Ray MD MPHil FMedSci , Ann Marie Navar MD, Phd , Steven E Nissen MD , Mariko Harada-Shiba MD, Phd , Danielle L. Curcio MBA , Annie Neild PhD , Douglas Kling MBA , Julie Butters BHSc, MBA , Brian A Ference MD, MPHIL, MSC , Ulrich Laufs MD , Maciej Banach MD PhD , Roxana Mehran MD , Alberico L Catapano PhD , Yong Huo MD , Michael H Davidson MD

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Abstract

Therapeutic Area

Pharmacologic Therapy

Background

Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that lowers low-density lipoprotein (LDL) cholesterol levels. The efficacy and safety of obicetrapib has not been fully characterized in patients at high risk of cardiovascular events.

Methods

BROADWAY enrolled 2530 patients with familial hypercholesterolemia (FH) or a history of atherosclerotic cardiovascular disease (ASCVD), treated with maximally tolerated lipid lowering therapy. Patients with either LDL cholesterol ³100 mg/deciliter and/or non-high-density lipoprotein (non-HDL) cholesterol ³130 mg/deciliter or LDL cholesterol 55-100 mg/deciliter and/or non-HDL cholesterol 85-130 mg/deciliter with at least one additional cardiovascular risk factor were randomized (2:1) to obicetrapib 10 mg or matching placebo daily for 365 days. The primary endpoint was the percent change from baseline to Day 84 in LDL cholesterol.

Results

Patients (mean age 65 years, female 33%, White race 74%, ASCVD 89%, FH 16%, statin use 90%) had a mean baseline LDL cholesterol level of 98 mg/deciliter. The difference between placebo and obicetrapib for the change in LDL cholesterol was -32.7% (95% confidence interval [CI] -35.8, -29.5), P<0.0001. The percent change from baseline in LDL cholesterol at day 84 was +2.7% (95% CI -0.4, 5.8) with placebo and -29.9% (95% CI -32.1, -27.8) with obicetrapib. The incidence of adverse events was similar across treatment groups.

Conclusions

Obicetrapib was well tolerated and produced placebo-adjusted LDL cholesterol reductions of 32.7% in patients at high risk of cardiovascular events with elevated lipid levels despite treatment with maximally tolerated lipid lowering therapy.

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obicetrapib在心血管高危患者中的安全性和有效性

治疗领域药物治疗背景dobicetrapib是一种高选择性胆固醇酯转移蛋白抑制剂，可降低低密度脂蛋白（LDL）胆固醇水平。obicetrapib在心血管事件高风险患者中的有效性和安全性尚未得到充分的表征。方法：百老汇纳入2530例家族性高胆固醇血症（FH）或有动脉粥样硬化性心血管疾病（ASCVD）病史的患者，接受最大耐受性降脂治疗。低密度脂蛋白胆固醇³100 mg/分升和/或非高密度脂蛋白（non-HDL）胆固醇³130 mg/分升或低密度脂蛋白胆固醇55-100 mg/分升和/或非高密度脂蛋白胆固醇85-130 mg/分升并至少有一个额外心血管危险因素的患者被随机分配（2:1）至obicetrapib 10 mg或匹配的安慰剂，每天365天。主要终点是LDL胆固醇从基线到第84天的变化百分比。结果患者（平均年龄65岁，女性33%，白人74%，ASCVD 89%, FH 16%，他汀类药物使用率90%）平均基线LDL胆固醇水平为98 mg/分升。安慰剂和obicetrapib在LDL胆固醇变化方面的差异为-32.7%(95%可信区间[CI] -35.8, -29.5), P<0.0001。与基线相比，第84天LDL胆固醇在安慰剂组的变化百分比为+2.7% (95% CI -0.4, 5.8)，在obicetrapib组的变化百分比为-29.9% （95% CI -32.1, -27.8）。各治疗组的不良事件发生率相似。结论sobicetrapib耐受性良好，在脂质水平升高的高危心血管事件患者中，尽管接受了最大耐受的降脂治疗，但仍能使LDL胆固醇降低32.7%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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