美国布列根和妇女医院Aruna Das Pradhan团队研究了Pemafibrate降低甘油三酯是否能降低心血管风险。相关论文于2022年11月5日发表在《新英格兰医学杂志》上。

高甘油三酯水平与心血管风险增加有关，但降低这些水平是否会降低心血管事件的发生率尚不确定。过氧化物酶体增殖物激活的选择性受体α调节剂Pemafibrate可降低甘油三酯水平并改善其他脂质水平。

在一项多国、双盲、随机、对照试验中，研究组将患有2型糖尿病、轻度至中度高甘油三酯血症（甘油三酯水平为200至499mg/dl）、高密度脂蛋白（HDL）胆固醇水平为40mg/dl或更低的患者分为两组，分别接受pemafibrate（0.2毫克，每日两次）或安慰剂治疗。

符合条件的患者正在接受指南指导的降脂治疗，或不能接受他汀类药物治疗而无不良反应，且低密度脂蛋白（LDL）胆固醇水平为100mg/dl或更低。主要疗效终点是非致命性心肌梗死、缺血性卒中、冠状动脉血运重建或心血管原因死亡的综合结局。

在10497名患者（66.9%既往有心血管疾病）中，基线空腹甘油三酯水平中位数为271mg/dl，高密度脂蛋白胆固醇水平为33mg/dl，低密度脂蛋白水平为78mg/dl。中位随访时间为3.4年。与安慰剂相比，pemafibrate对4个月时血脂水平的影响为：甘油三酯降低26.2%，极低密度脂蛋白（VLDL）胆固醇降低25.8%，残余胆固醇（脂肪分解和脂蛋白重塑后富含甘油三酯的脂蛋白转运的胆固醇）降低25.6%，载脂蛋白C-III降低27.6%，载脂蛋白B降低4.8%。

Pemafibrate组中有572名患者发生主要终点事件，安慰剂组有560名患者（危险比为1.03），在任何预先指定的亚组中均无明显疗效改变。两组之间严重不良事件的总体发生率没有显著差异，但pemafibrate与较高的肾脏不良事件和静脉血栓栓塞发生率以及较低的非酒精性脂肪性肝病发生率相关。

研究结果表明，在患有2型糖尿病、轻度至中度高甘油三酯血症以及低HDL和低LDL胆固醇水平的患者中，尽管pemafibrate降低了甘油三酯、VLDL胆固醇、残余胆固醇和载脂蛋白C-III水平，但接受pemafibrate治疗患者的心血管事件发生率并不低于接受安慰剂治疗的患者。

附：英文原文

Title: Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk | NEJM

Author: Aruna Das Pradhan, M.D., M.P.H.,, Robert J. Glynn, Sc.D.,, Jean-Charles Fruchart, Ph.D.,, Jean G. MacFadyen, B.A.,, Elaine S. Zaharris, B.A.,, Brendan M. Everett, M.D., M.P.H.,, Stuart E. Campbell, B.A.,, Ryu Oshima, M.S., R.Ph.,, Pierre Amarenco, M.D.,, Dirk J. Blom, M.D., Ph.D.,, Eliot A. Brinton, M.D.,, Robert H. Eckel, M.D.,, Marshall B. Elam, M.D., Ph.D.,, Joo S. Felicio, M.D., Ph.D.,, Henry N. Ginsberg, M.D.,, Assen Goudev, M.D.,, Shun Ishibashi, M.D., Ph.D.,, Jacob Joseph, M.D.,, Tatsuhiko Kodama, M.D., Ph.D.,, Wolfgang Koenig, M.D.,, Lawrence A. Leiter, M.D.,, Alberto J. Lorenzatti, M.D.,, Boris Mankovsky, M.D.,, Nikolaus Marx, M.D.,, Brge G. Nordestgaard, M.D., D.M.S.C.,, Dénes Páll, M.D.,, Kausik K. Ray, M.D.,, Raul D. Santos, M.D., Ph.D.,, Handrean Soran, M.D.,, Andrey Susekov, M.D., Ph.D., D.Sc.,, Michal Tendera, M.D.,, Koutaro Yokote, M.D., Ph.D.,, Nina P. Paynter, Ph.D.,, Julie E. Buring, Sc.D.,, Peter Libby, M.D.,, and Paul M Ridker, M.D., M.P.H.

Issue&Volume: 2022-11-05

Abstract:

Background

High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator–activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.

Methods

In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes.

Results

Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were 26.2% for triglycerides, 25.8% for very-low-density lipoprotein (VLDL) cholesterol, 25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), 27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease.

Conclusions

Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels.

DOI: 10.1056/NEJMoa2210645

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2210645