Global guidelines for the management of high-cardiovascular-risk patients include aggressive goals for low-density lipoprotein cholesterol (LDL-C). Statin therapy alone is often insufficient to reach goals and nonstatin options have limitations. Here, we tested the lipid-lowering effects of the cholesteryl ester transfer protein (CETP) inhibitor drug obicetrapib in a randomized, double-blind, placebo-controlled trial in dyslipidaemic patients (n = 120, median LDL-C 88 mg dl⁻¹) with background high-intensity statin treatment (NCT04753606). Over the course of 8 weeks, treatment with 5 mg or 10 mg obicetrapib resulted in a significant decrease as compared with placebo in median LDL-C concentration (by up to 51%; P < 0.0001), the primary trial outcome. As compared with placebo, obicetrapib treatment also significantly (P < 0.0001) decreased apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) concentration (by up to 44%), and significantly (P < 0.0001) increased HDL-C concentration (by up to 165%; the secondary trial outcomes) and had an acceptable safety profile. These results support the potential of obicetrapib to address an unmet medical need for high-cardiovascular-risk patients.

高心血管风险患者管理的全球指南包括低密度脂蛋白胆固醇 (LDL-C) 的积极目标。单独的他汀类药物治疗通常不足以达到目标，非他汀类药物的选择也有局限性。在这里，我们在一项针对血脂异常患者的随机、双盲、安慰剂对照试验中测试了胆固醇酯转移蛋白 (CETP) 抑制剂药物 obicetrapib 的降脂作用（n  = 120，中位 LDL-C 88 mg dl ^-1 ) 与背景高强度他汀类药物治疗 (NCT04753606)。在 8 周的过程中，与安慰剂相比，使用 5 mg 或 10 mg obicetrapib 治疗导致中位 LDL-C 浓度显着下降（高达 51%；P < 0.0001)，主要试验结果。与安慰剂相比，obicetrapib 治疗还显着（P  < 0.0001）降低了载脂蛋白 B（高达 30%）和非高密度脂蛋白胆固醇（non-HDL-C）浓度（高达 44%），并且显着( P  < 0.0001) 增加 HDL-C 浓度（高达 165%；次要试验结果）并具有可接受的安全性。这些结果支持 obicetrapib 解决高心血管风险患者未满足的医疗需求的潜力。