Supplementary Material for: Risk of Ischemic Stroke in High Risk Atrial Fibrillation Patients during Periods of Warfarin Discontinuation for Surgical Procedures

Importance: The risk of ischemic stroke during periods of warfarin discontinuation for surgical procedures is recognized but not well characterized. Objective: The study aimed to quantitate the risk of ischemic stroke associated with high risk atrial fibrillation during periods of warfarin discontinuation. Design, Setting and Participants: A cohort of 4,060 patients (mean follow-up period of 3.5 ± 1.3 years) were randomized into the Atrial Fibrillation Follow-Up Investigation of Rhythm Management study. Patients enrolled in the study had atrial fibrillation plus at least one other risk factor for stroke or death: age ≥65 years', systemic hypertension, diabetes mellitus, congestive heart failure, transient ischemic attack, prior stroke, left atrium >50 mm, left ventricular fractional shortening Exposure: Warfarin discontinuation for procedure. Main Outcome and Measures: The association of warfarin discontinuation with the incidence of ischemic stroke using pooled repeated measures and Cox proportional hazards analyses during follow-up after adjusting for age, gender, obesity, diabetes mellitus, hypercholesterolemia, cigarette smoking and study period. Results: Warfarin discontinuation for procedure occurred in 265 (0.4%) of the 71,355 person observations. Compared with those without warfarin discontinuation, the rate of ischemic stroke was higher among participants with surgery-related warfarin discontinuation (1.1% of 265 person observations vs. 0.2% of 71,090 person observations, p = 0.001). Warfarin discontinuation was associated with an increased risk for ischemic stroke (relative risk 5.8; 95% CI 1.8-18.4) after adjusting for potential confounders. The population-attributable risk associated with surgery-related warfarin discontinuation was estimated to be 23.1% (95% CI 15.2-30.9%) for ischemic stroke. Conclusions and Relevance: The 6-fold higher risk of ischemic stroke associated with discontinuation of warfarin for surgical procedures must be recognized in high risk atrial fibrillation patients and considered in the risk-benefit analysis of any procedure.

研究背景：外科手术期间停用华法林（warfarin）所致缺血性卒中风险已被学界识别，但该风险的具体特征尚未得到充分阐明。研究目的：本研究旨在量化高危心房颤动（atrial fibrillation）患者在华法林停用期间的缺血性卒中发生风险。研究设计、研究场景与研究对象：本队列共纳入4060例患者，平均随访时长为3.5±1.3年，所有受试者均来自《心房颤动节律管理随访研究（Atrial Fibrillation Follow-Up Investigation of Rhythm Management）》。入组患者均患有心房颤动，且至少合并1项卒中或死亡风险因素：年龄≥65岁、系统性高血压、糖尿病、充血性心力衰竭、短暂性脑缺血发作、既往卒中史、左心房直径＞50mm、左心室短轴缩短分数（left ventricular fractional shortening）。暴露因素：因外科手术停用华法林。主要结局与评估指标：本研究采用合并重复测量分析与Cox比例风险回归分析（Cox proportional hazards analyses），在校正年龄、性别、肥胖、糖尿病、高胆固醇血症、吸烟状况及研究周期等混杂因素后，分析华法林停用与随访期间缺血性卒中发生率之间的关联。研究结果：在71355人-年的随访观察中，共有265例（占总观察人次的0.4%）患者因手术停用华法林。与未停用华法林的受试者相比，手术相关华法林停用者的缺血性卒中发生率更高：265例人-年观察中的卒中发生率为1.1%，而71090例人-年观察中的发生率为0.2%（p=0.001）。在校正潜在混杂因素后，华法林停用与缺血性卒中风险升高显著相关（相对风险（relative risk）为5.8；95%置信区间（95% CI）：1.8~18.4）。手术相关华法林停用对应的缺血性卒中人群归因风险估计为23.1%（95% CI：15.2%~30.9%）。结论与临床意义：高危心房颤动患者因外科手术停用华法林时，缺血性卒中风险升高6倍，这一临床风险需得到充分重视，且应在任何手术的风险-获益分析中予以考量。