依泽替米贝在 REDUCE-IT 试验中伴有和不伴有房颤患者的心血管获益

Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillation in REDUCE-IT.

机构信息

Department of Medicine University of Iowa Iowa City IA USA.

Mount Sinai Heart Icahn School of Medicine at Mount Sinai Health System New York NY USA.

出版信息

J Am Heart Assoc. 2023 Mar 7;12(5):e026756. doi: 10.1161/JAHA.121.026756. Epub 2023 Feb 21.

Background In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization, but was associated with increased atrial fibrillation/atrial flutter (AF) hospitalization (3.1% IPE versus 2.1% placebo; =0.004). Methods and Results We performed post hoc efficacy and safety analyses of patients with or without prior AF (before randomization) and with or without in-study time-varying AF hospitalization to assess relationships of IPE (versus placebo) and outcomes. In-study AF hospitalization event rates were higher in patients with prior AF (12.5% versus 6.3%, IPE versus placebo; =0.007) versus without prior AF (2.2% versus 1.6%, IPE versus placebo; =0.09). Serious bleeding rates trended higher in patients with (7.3% versus 6.0%, IPE versus placebo; =0.59) versus without prior AF (2.3% versus 1.7%, IPE versus placebo; =0.08). With IPE, serious bleeding trended higher regardless of prior AF (interaction value []=0.61) or postrandomization AF hospitalization (=0.66). Patients with prior AF (n=751, 9.2%) versus without prior AF (n=7428, 90.8%) had similar relative risk reductions of the primary composite and key secondary composite end points with IPE versus placebo (=0.37 and =0.55, respectively). Conclusions In REDUCE-IT, in-study AF hospitalization rates were higher in patients with prior AF especially in those randomized to IPE. Although serious bleeding trended higher in those randomized to IPE versus placebo over the course of the study, serious bleeding was not different regardless of prior AF or in-study AF hospitalization. Patients with prior AF or in-study AF hospitalization had consistent relative risk reductions across primary, key secondary, and stroke end points with IPE. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01492361; Unique Identifier: NCT01492361.

背景在 REDUCE-IT（依泽替米贝降低心血管事件试验）中，与安慰剂相比，icosapent ethyl（IPE）降低了心血管死亡、心肌梗死、卒中和冠状动脉血运重建或需要住院的不稳定型心绞痛，但与心房颤动/心房扑动（AF）住院治疗的增加相关（3.1%的 IPE 与 2.1%的安慰剂；=0.004）。

方法和结果我们对有或无先前 AF（随机前）以及有或无研究期间时间变化的 AF 住院治疗的患者进行了事后疗效和安全性分析，以评估 IPE（与安慰剂相比）与结局的关系。先前有 AF 的患者（12.5%与 6.3%，IPE 与安慰剂；=0.007）与无先前 AF 的患者（2.2%与 1.6%，IPE 与安慰剂；=0.09）相比，研究期间 AF 住院治疗事件发生率更高。有严重出血史的患者（7.3%与 6.0%，IPE 与安慰剂；=0.59）与无严重出血史的患者（2.3%与 1.7%，IPE 与安慰剂；=0.08）相比，严重出血的发生率呈上升趋势。无论是否存在先前的 AF（交互值 []=0.61）或随机后 AF 住院治疗（=0.66），IPE 治疗时严重出血的发生率均呈上升趋势。与无先前 AF 的患者（n=7428，90.8%）相比，先前有 AF 的患者（n=751，9.2%）使用 IPE 治疗时主要复合终点和关键次要复合终点的相对风险降低相似（=0.37 和 =0.55）。

结论在 REDUCE-IT 中，先前有 AF 的患者的研究期间 AF 住院治疗率较高，尤其是随机接受 IPE 治疗的患者。尽管在整个研究过程中，与安慰剂相比，接受 IPE 治疗的患者严重出血的趋势更高，但无论是否存在先前的 AF 或研究期间的 AF 住院治疗，严重出血并无差异。先前有 AF 或研究期间有 AF 住院治疗的患者，使用 IPE 治疗时，主要终点、关键次要终点和卒中等终点的相对风险降低一致。