Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics
Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics
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DOI：
10.1093/eurheartj/ehz778
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发表时间：
2020-06-21
影响因子：
39.3
通讯作者：
Luescher, Thomas F.
中科院分区：
文献类型：
--
作者：
Boden, William E.;Bhatt, Deepak L.;Luescher, Thomas F.
本临床综述的目的是：(1)强调基线甘油三酯(TG)升高在控制良好的低密度脂蛋白胆固醇(LDL-C)水平方面的重要性；(2)介绍他汀类药物作为动脉粥样硬化性心血管疾病(ASCVD)残余风险的主要促成因素，特别是在患有2型糖尿病、代谢综合征和肥胖症的患者中，这些患者的独特脂类表型无法仅用低密度脂蛋白-C降低疗法进行最佳治疗；(Ii)描述具有里程碑意义的RECLE-IT试验的结果和临床意义，在该试验中，二十碳五烯酸乙酯显著改善了ASCVD的结果。虽然许多遗传学研究表明，甘油三酯升高是ASCVD的一个独立原因，但先前使用烟酸、贝特类、omega-3脂肪酸和膳食补充剂鱼油制剂的安慰剂对照试验未能显示出在他汀类药物治疗的基础上显著减少心血管事件。相比之下，在8 179名参与者中进行的Reduce-IT试验令人信服地表明，在ASCVD的高危患者中，每天服用4g二十碳五烯酸乙酯(二十碳五烯酸乙酯)可显著减少试验主要终点和多个预先指定的次要终点的事件，包括心血管死亡，以及后续和全部主要终点和关键次要终点事件。在他汀类药物治疗的基础上，二十碳五烯酸乙酯明确地减少了ASCVD事件的发生。RECESS-IT试验的结果应该会改变我们管理不断增长的高甘油三酯血症患者的方法，这些患者的血脂表型需要更多的强化治疗，而不仅仅是降低低密度脂蛋白。
The aims of this clinical review are to: (i) highlight the importance of elevated baseline triglycerides (TG) in the setting of well-controlled low-density lipoprotein cholesterol (LDL-C) on statins as a major contributor to residual atherosclerotic cardiovascular disease (ASCVD) risk, particularly among patients with type 2 diabetes mellitus, metabolic syndrome, and obesity whose distinctive lipid phenotype cannot be optimally treated with LDL-C reduction therapy alone; (ii) describe the findings and clinical implications of the landmark REDUCE-IT trial in which ethyl eicosapentaenoic acid significantly improved ASCVD outcomes. While many genetic studies have shown that elevated TG are an independent causal factor for ASCVD, prior placebo-controlled trials using niacin, fibrates, omega-3 fatty acids, and dietary supplement fish oil preparations have failed to demonstrate significant CV event reduction when added to statin therapy. In contrast, the REDUCE-IT trial in 8179 participants showed convincingly that the administration of 4 g daily of icosapent ethyl (an ethyl ester of eicosapentaenoic acid) in patients at high risk for ASCVD with increased levels of baseline TG [median value, 2.44 mmol/L (216.0 mg/dL)] but well-controlled LDL-C [median value, 1.94 mmol/L (75.0 mg/dL)] reduced significantly incident events across both the trial primary endpoint and multiple prespecified secondary endpoints, including cardiovascular death, as well as both subsequent and total primary endpoint and key secondary endpoint events. Icosapent ethyl unequivocally contributed to ASCVD event reduction over and above statin therapy. The REDUCE-IT trial results should alter our approach to managing a growing population of hypertriglyceridaemic patients whose lipid phenotype requires more intensive treatment beyond LDL-C lowering alone.