Background:Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function.Methods:REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135–499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke).Results:Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL·min^–1·1.73 m^–2 (range, 17–123 mL·min^–1·1.73 m^–2). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR <60 mL·min^–1·1.73 m^–2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59–0.85]; P=0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57–0.88]; P=0.001). The numeric reduction in cardiovascular death was greatest in the eGFR <60 mL·min^–1·1.73 m^–2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51–0.95]; P=0.02). Although patients with eGFR <60 mL·min^–1·1.73 m^–2 treated with icosapent ethyl had the highest numeric rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86–2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90–2.18]; P=0.13), HRs for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter=0.92; P-interaction for serious bleeding=0.76).Conclusions:In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361

中文翻译：

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Icosapent Ethyl 在已确诊的心血管疾病或糖尿病患者的肾功能范围内的益处：REDUCE-IT RENAL

背景：慢性肾病与已确诊的心血管疾病 (CVD) 或糖尿病患者的不良结局相关。用于治疗 CVD 的常用药物在肾功能下降的患者中效果较差。方法：REDUCE-IT（使用二十碳五烯乙基干预试验减少心血管事件）是一项多中心、双盲、安慰剂对照试验，随机分配他汀类药物-治疗甘油三酯升高（135-499 mg/dL）的患者，这些患者患有 CVD 或糖尿病，并且使用 icosapent ethyl（每天 4 g）或安慰剂治疗有 1 个额外的危险因素。来自 REDUCE-IT 的患者按照预先设定的估计肾小球滤过率 (eGFR) 类别进行分类，以分析 icosapent ethyl 对主要终点（心血管死亡、非致死性心肌梗死、^–1 ·1.73 m ^–2（范围，17–123 mL·min ^–1 ·1.73 m ^–2）。在研究访问期间，icosapent ethyl 与安慰剂的中位 eGFR 没有有意义的变化。使用 icosapent ethyl 治疗导致基线 eGFR 类别的主要和关键次要复合终点持续减少。eGFR <60 mL·min ^–1 ·1.73 m ^{–2 的}患者在主要复合终点方面具有最大的绝对和相似的相对风险降低（icosapent ethyl 与安慰剂，21.8% 与 28.9%；风险比 [HR ]，0.71 [95% CI，0.59–0.85]；P = 0.0002) 和关键的次要复合终点（16.8% 对 22.5%；HR 0.71 [95% CI，0.57–0.88]；P = 0.001)。在 eGFR <60 mL·min ^–1 ·1.73 m ^–2组中心血管死亡的数值降低最大（乙基二十碳五烯酸：7.6%；安慰剂：10.6%；HR，0.70 [95% CI，0.51–0.95]；P =0.02)。尽管 eGFR <60 mL·min ^–1 ·1.73 m ^{–2 的}患者用 icosapent ethyl 治疗的心房颤动/扑动率最高（icosapent ethyl：4.2%；安慰剂 3.0%；HR 1.42 [95% CI，0.86– 2.32]；P = 0.17）和严重出血（乙基二十碳五烯酸：5.4%；安慰剂 3.6%；HR，1.40 [95% CI，0.90-2.18]；P = 0.13），心房颤动/扑动和严重出血的 HR 相似跨 eGFR 类别 ( P-房颤/扑动的相互作用=0.92；严重出血的P-相互作用 = 0.76)。结论：在 REDUCE-IT 中，icosapent ethyl 减少了广泛的基线 eGFR 类别中的致命和非致命缺血事件。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT01492361