澳大利亚莫纳什大学Stephen J. Nicholls团队近期取得重要工作进展，他们完成了CETP抑制剂obicetrapib与高强度他汀类药物联合使用的降血脂效果的2期临床试验。该项研究成果2022年8月11日在线出版于《自然—医学》杂志上。

研究人员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，5 mg或10 mg obicetrapib治疗导致中位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，obicetrapib 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%），并且显著（P < 0.0001）增加了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在解决高心血管风险患者未被满足的医疗需求方面的潜力。

据了解，管理高心血管风险患者的全球指南包括低密度脂蛋白胆固醇（LDL-C）的积极目标。他汀类药物单独治疗往往不足以达到目标，非他汀类药物的选择也有局限性。

附：英文原文

Title: Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial

Author: Nicholls, Stephen J., Ditmarsch, Marc, Kastelein, John J., Rigby, Scott P., Kling, Douglas, Curcio, Danielle L., Alp, Nicholas John, Davidson, Michael H.

Issue&Volume: 2022-08-11

Abstract: 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 88mgdl1) with background high-intensity statin treatment (NCT04753606). Over the course of 8 weeks, treatment with 5mg or 10mg 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.

DOI: 10.1038/s41591-022-01936-7

Source: https://www.nature.com/articles/s41591-022-01936-7