Douketis James D, Spyropoulos Alex C, Duncan Joanne, Carrier Marc, Le Gal Gregoire, Tafur Alfonso J, Vanassche Thomas, Verhamme Peter, Shivakumar Sudeep, Gross Peter L, Lee Agnes Y Y, Yeo Erik, Solymoss Susan, Kassis Jeannine, Le Templier Geneviève, Kowalski Stephen, Blostein Mark, Shah Vinay, MacKay Elizabeth, Wu Cynthia, Clark Nathan P, Bates Shannon M, Spencer Frederick A, Arnaoutoglou Eleni, Coppens Michiel, Arnold Donald M, Caprini Joseph A, Li Na, Moffat Karen A, Syed Summer, Schulman Sam
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Medicine, Northwell Health at Lenox Hill Hospital, New York, New York.
JAMA Intern Med. 2019 Nov 1;179(11):1469-1478. doi: 10.1001/jamainternmed.2019.2431.
Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain.
To investigate the safety of a standardized perioperative DOAC management strategy.
DESIGN, SETTING, AND PARTICIPANTS: The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol.
A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low-bleeding-risk procedure and 2 to 3 days after a high-bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation.
Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level (<50 ng/mL) at the time of the procedure.
The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high-bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high-bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort.
In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.
使用直接口服抗凝剂（DOAC）并要求进行择期手术或操作的心房颤动（AF）患者呈现出一种常见的临床情况，但围手术期管理尚不确定。
研究标准化围手术期DOAC管理策略的安全性。
设计、地点和参与者：在加拿大、美国和欧洲的23个临床中心进行的围手术期抗凝用于手术评估（PAUSE）队列研究，于2014年8月1日至2018年7月31日招募并筛选患者。参与者（n = 3007）患有AF；年龄在18岁及以上；长期使用阿哌沙班、达比加群酯或利伐沙班；计划进行择期手术或操作；并且能够遵守DOAC治疗中断方案。
基于DOAC药代动力学特性、手术相关出血风险和肌酐清除率水平的简单标准化围手术期DOAC治疗中断和恢复策略。对于低出血风险手术，在手术前1天停用DOAC方案；对于高出血风险手术，在手术前2天停用DOAC方案。对于低出血风险手术，在手术后1天恢复DOAC方案；对于高出血风险手术，在手术后2至3天恢复DOAC方案。对患者进行术后30天的随访。
主要出血和动脉血栓栓塞（缺血性卒中、全身性栓塞和短暂性脑缺血发作）以及手术时抗凝剂水平不可检测或残留极少（<50 ng/mL）的患者比例。
3007例AF患者（平均[标准差]年龄为72.5[9.39]岁；1988例男性[66.1%]）中，阿哌沙班组有1257例（41.8%），达比加群组有668例（22.2%），利伐沙班组有1082例（36.0%）；1007例患者（33.5%）进行了高出血风险手术。阿哌沙班组术后30天主要出血发生率为1.35%（95%CI，0% - 2.00%），达比加群组为0.90%（95%CI，0% - 1.73%），利伐沙班组为1.85%（95%CI，0% - 2.65%）。动脉血栓栓塞发生率在阿哌沙班组为0.16%（95%CI，0% - 0.48%），达比加群组为0.60%（95%CI，0% - 1.33%），利伐沙班组为0.37%（95%CI，0% - 0.82%）。在进行高出血风险手术的患者中，阿哌沙班组主要出血发生率为2.96%（95%CI，0% - 4.68%），利伐沙班组为2.95%（95%CI，0% - 4.76%）。
在本研究中，因择期手术或操作而中断DOAC治疗的AF患者，一种不进行肝素桥接或凝血功能检测的围手术期管理策略与低主要出血和动脉血栓栓塞发生率相关。
