Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial.
Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial.
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DOI：
10.1002/clc.22692
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发表时间：
2017-03
影响因子：
2.7
通讯作者：
REDUCE-IT Investigators
中科院分区：
文献类型：
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作者：
Bhatt DL;Steg PG;Brinton EA;Jacobson TA;Miller M;Tardif JC;Ketchum SB;Doyle RT Jr;Murphy SA;Soni PN;Braeckman RA;Juliano RA;Ballantyne CM;REDUCE-IT Investigators
尽管使用他汀类药物，残余心血管风险仍然存在，但除低密度脂蛋白胆固醇（LDL-C）外的脂质靶向治疗的结局研究尚未显示出额外的益处。甘油三酯升高是心血管事件的独立危险因素。高剂量的二十碳五烯酸（EPA）可降低富含甘油三酯的脂蛋白，而不会升高LDL-C。Omega-3具有多效性心脏保护益处，而不仅仅是降低甘油三酯。到目前为止，还没有大型的、多国的、随机的临床试验证明在他汀类药物治疗的基础上降低甘油三酯可以改善心血管结局。Icosapent Ethyl减少心血管事件干预试验（REDUCE‐IT; NCT 01492361）是一项比较Icosapent Ethyl（一种高度纯化的EPA乙酯）与安慰剂的3b期随机、双盲、安慰剂对照试验。主要目的是评价二十碳五烯酸乙酯治疗是否能减少他汀类药物治疗的高甘油三酯心血管风险升高患者的缺血事件。REDUCE‐IT入组了年龄≥45岁且已确诊心血管疾病或年龄≥50岁且患有糖尿病和1个额外风险因素的男性或女性。随机化要求在合格测量前空腹甘油三酯≥150 mg/dL且<500 mg/dL，LDL-C>40 mg/dL且≤100 mg/dL，且他汀类药物（±依折麦布）稳定≥4周。主要终点是心血管死亡、非致死性心肌梗死、非致死性卒中、冠状动脉血运重建或不稳定型心绞痛的复合终点。关键次要终点是心血管死亡、非致死性心肌梗死或非致死性卒中的复合终点。将评估几个次要、三级和探索性终点。在全球约470家中心，约8000例患者接受了随机化。将在该事件驱动试验中继续随访，直至发生约1612起经裁定的主要疗效终点事件。
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol (LDL‐C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High‐dose eicosapentaenoic acid (EPA) reduces triglyceride‐rich lipoproteins without raising LDL‐C. Omega‐3s have postulated pleiotropic cardioprotective benefits beyond triglyceride‐lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE‐IT; NCT01492361) is a phase 3b randomized, double‐blinded, placebo‐controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin‐treated patients with high triglycerides at elevated cardiovascular risk. REDUCE‐IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/dL and <500 mg/dL and LDL‐C >40 mg/dL and ≤100 mg/dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow‐up will continue in this event‐driven trial until approximately 1612 adjudicated primary‐efficacy endpoint events have occurred.