Victorian Heart Institute, Monash University, Clayton, Victoria, Australia.
NewAmsterdam Pharma B.V., Naarden, Netherlands.
Nat Med. 2022 Aug;28(8):1672-1678. doi: 10.1038/s41591-022-01936-7. Epub 2022 Aug 11.
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) 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.
全球高心血管风险患者管理指南包括对低密度脂蛋白胆固醇（LDL-C）的积极目标。单独使用他汀类药物通常不足以达到目标，而非他汀类药物存在局限性。在这里，我们在接受高强度他汀类药物治疗的血脂异常患者（n=120，中位 LDL-C 88mg/dl）中进行了一项随机、双盲、安慰剂对照试验，测试了胆固醇酯转移蛋白（CETP）抑制剂药物奥利西贝特的降脂效果（NCT04753606）。在 8 周的时间里，与安慰剂相比，5mg 或 10mg 奥利西贝特治疗可使中位 LDL-C 浓度显著降低（高达 51%；P<0.0001），这是主要试验结果。与安慰剂相比，奥利西贝特治疗还显著（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（非-HDL-C）浓度（高达 44%），并显著（P<0.0001）增加了高密度脂蛋白胆固醇（HDL-C）浓度（高达 165%），这是次要试验结果），且具有可接受的安全性特征。这些结果支持奥利西贝特有可能解决高心血管风险患者未满足的医疗需求。
