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替格瑞洛治疗的急性冠脉综合征患者早期与延迟搭桥手术:RAPID CABG随机开放标签非劣效性试验

Early vs Delayed Bypass Surgery in Patients With Acute Coronary Syndrome Receiving Ticagrelor: The RAPID CABG Randomized Open-Label Noninferiority Trial.

作者信息

So Derek Y F, Wells George A, Lordkipanidzé Marie, Chong Aun Yeong, Ruel Marc, Perrault Louis P, Le May Michel R, Sun Louise, Tran Diem, Labinaz Marino, Glover Christopher, Russo Juan, Welman Mélanie, Chan Vincent, Chen Lily, Bernick Jordan, Rubens Fraser, Tanguay Jean-Francois

机构信息

Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Cardiovascular Research Methods Centre, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

出版信息

JAMA Surg. 2025 Apr 1;160(4):387-394. doi: 10.1001/jamasurg.2024.7066.

Abstract

IMPORTANCE

Perioperative bleeding is a major concern in patients receiving ticagrelor for acute coronary syndromes (ACS) when coronary artery bypass graft (CABG) surgery is required.

OBJECTIVE

To evaluate whether early CABG surgery at 2 to 3 days after ticagrelor cessation is noninferior to waiting 5 to 7 days.

DESIGN, SETTING, AND PARTICIPANTS: RAPID CABG was a noninferiority, open-label randomized trial with 6 months of follow-up. Participants were patients with ACS who had received ticagrelor and required CABG. Patients were enrolled in tertiary centers in Canada between January 2016 and March 2021. Data were analyzed from March 2021 to December 2023.

INTERVENTION

Early or delayed CABG.

MAIN OUTCOMES AND MEASURES

The primary outcome was based on noninferiority comparison of class 3 or 4 universal definition of perioperative bleeding (UDPB). Noninferiority was prespecified as 8% between groups. Twelve-hour chest tube drainage was reported as a noninferiority comparison. Other bleeding, ischemic, and length-of-stay outcomes were assessed for superiority.

RESULTS

Among 143 randomized patients, the median (IQR) age was 65 (58-72) years; there were 117 male patients (82%) and 26 female (18%). Of these, 123 patients (86.0%) underwent surgery in the allocated time frame (per protocol). The median (IQR) time to surgery was 3 (2-3) days in the early group and 6 (5-7) days in the delayed group (P < .001). In a per-protocol analysis, severe or massive UDPB occurred in 3 of 65 early-group patients (4.6%) and 3 of 58 patients (5.2%) in the delayed group (between-group difference, -0.6%; 95% CI, -8.3% to 7.1%; P = .03 for noninferiority). Median (IQR) chest tube drainage was 470 (330-650) mL vs 495 (380-610) mL (between-group difference -25 mL; 95% CI, -111.25 to 35; P = .01 for noninferiority). Median (IQR) hospital stay was 9 (7-13) days and 12 (10-15) days for the early and delayed groups (P < .001).

CONCLUSION AND RELEVANCE

This study found that an early surgical strategy, 2 to 3 days after ticagrelor cessation, was noninferior in incurring perioperative bleeding. The data support a reduction in the delay between ticagrelor cessation and CABG surgery and may decrease hospital length of stay.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT02668562.

摘要

重要性

对于因急性冠状动脉综合征(ACS)接受替格瑞洛治疗且需要进行冠状动脉旁路移植术(CABG)的患者,围手术期出血是一个主要问题。

目的

评估在停用替格瑞洛后2至3天进行早期CABG手术是否不劣于等待5至7天。

设计、设置和参与者:RAPID CABG是一项非劣效性、开放标签的随机试验,随访6个月。参与者为接受替格瑞洛治疗且需要CABG的ACS患者。2016年1月至2021年3月期间,患者在加拿大的三级中心入组。2021年3月至2023年12月对数据进行分析。

干预措施

早期或延迟CABG。

主要结局和衡量指标

主要结局基于围手术期出血通用定义(UDPB)3级或4级的非劣效性比较。组间非劣效性预先设定为8%。报告12小时胸管引流量作为非劣效性比较。评估其他出血、缺血和住院时间结局的优越性。

结果

143例随机分组患者中,年龄中位数(IQR)为65(58 - 72)岁;男性患者117例(82%),女性患者26例(18%)。其中,123例患者(86.0%)在分配的时间范围内接受手术(符合方案)。早期组手术时间中位数(IQR)为3(2 - 3)天,延迟组为6(5 - 7)天(P <.001)。在符合方案分析中,早期组65例患者中有3例(4.6%)发生严重或大量UDPB,延迟组58例患者中有3例(5.2%)发生(组间差异为 - 0.6%;95% CI, - 8.3%至7.1%;非劣效性P = 0.03)。胸管引流中位数(IQR)为470(330 - 650)mL 对比495(380 - 610)mL(组间差异 - 25 mL;95% CI, - 111.25至35;非劣效性P = 0.01)。早期组和延迟组住院时间中位数(IQR)分别为9(7 - 13)天和12(10 - 15)天(P <.001)。

结论及相关性

本研究发现,在停用替格瑞洛后2至3天的早期手术策略在围手术期出血方面不劣。数据支持缩短停用替格瑞洛与CABG手术之间的延迟时间,并可能缩短住院时间。

试验注册

ClinicalTrials.gov标识符:NCT02668562

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