Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Blalock 524-C, Baltimore, MD, 21287, USA.
Center for Cardiovascular Disease Prevention, Cardiovascular Division, Baylor Scott and White Health Heart Hospital Baylor Plano, Plano, TX, USA.
Curr Atheroscler Rep. 2022 Oct;24(10):767-778. doi: 10.1007/s11883-022-01052-4. Epub 2022 Jul 27.
Mounting evidence continues to support the causal role of triglyceride-rich lipoproteins (TRL) in the development of atherosclerotic cardiovascular disease (ASCVD). Substantial residual ASCVD risk remains among high-risk patients who have elevated triglycerides despite reduction in low-density lipoprotein cholesterol (LDL-C) with statin therapy. Ongoing research efforts have focused on evaluating triglyceride-lowering therapies among patients with hypertriglyceridemia.
The REDUCE-IT trial showed that the addition of icosapent ethyl, a highly purified form of eicosapentaenoic acid (EPA), can reduce vascular events among statin-treated individuals with elevated triglycerides who have either clinical ASCVD or diabetes plus another risk factor. Although additional evidence for EPA has emerged from other trials, conflicting results have been reported by subsequent trials that tested different omega-3 fatty acid formulations. Randomized clinical trials have not demonstrated incremental ASCVD benefit of fibrates on background of statin therapy, but fibrates are used to help prevent pancreatitis in patients with severe hypertriglyceridemia. Selective inhibitors of apolipoprotein C-III (apoC3) and angiopoietin-like protein 3 (ANGPTL3), proteins that are involved in metabolism of TRLs by regulating lipoprotein lipase, have been tested in selected patient populations and showed significant reduction in triglyceride and LDL-C levels. Statin therapy continues to be the cornerstone of pharmacologic reduction of cardiovascular risk. High-dose EPA in the form of icosapent ethyl has been demonstrated to have cardiovascular benefit on top of statins in persons with elevated triglycerides at high ASCVD risk. Ongoing clinical trials are evaluating novel selective therapies such as apoC3 and ANGPTL3 inhibitors.
越来越多的证据表明富含甘油三酯的脂蛋白(TRL)在动脉粥样硬化性心血管疾病(ASCVD)的发展中起因果作用。尽管用他汀类药物治疗降低了低密度脂蛋白胆固醇(LDL-C),但高风险患者的甘油三酯升高,仍存在大量剩余的 ASCVD 风险。目前的研究重点是评估高甘油三酯血症患者的降甘油三酯治疗。
REDUCE-IT 试验表明,在他汀类药物治疗后甘油三酯升高的同时患有临床 ASCVD 或糖尿病加另一个危险因素的患者中,添加高度纯化的二十碳五烯酸(EPA)依泽替米贝可降低血管事件。尽管其他试验也提供了更多关于 EPA 的证据,但随后的试验报告了相互矛盾的结果,这些试验测试了不同的 ω-3 脂肪酸配方。随机临床试验并未证明贝特类药物在他汀类药物治疗背景下对 ASCVD 的额外获益,但贝特类药物用于预防严重高甘油三酯血症患者的胰腺炎。载脂蛋白 C-III(apoC3)和血管生成素样蛋白 3(ANGPTL3)的选择性抑制剂,这些蛋白通过调节脂蛋白脂肪酶参与 TRL 的代谢,已在选定的患者人群中进行了测试,并显示甘油三酯和 LDL-C 水平显著降低。他汀类药物治疗仍然是降低心血管风险的药物治疗基石。高剂量 EPA 以依泽替米贝的形式在高 ASCVD 风险的高甘油三酯血症患者中除了他汀类药物之外还具有心血管获益。正在进行的临床试验正在评估新型选择性治疗方法,如 apoC3 和 ANGPTL3 抑制剂。