Supplementary Material for: Warfarin Use, Stroke, and Bleeding Risk among Pre-Existing Atrial Fibrillation US Veterans Transitioning to Dialysis

<b><i>Introduction:</i></b> Anticoagulation is commonly used for stroke prevention among patients with atrial fibrillation (AF); however, end-stage renal disease (ESRD) patients on hemodialysis are at higher risk of bleeding and stroke, even without anticoagulation. It is unclear if patients should be continued on anticoagulation at the time of transition to ESRD. In this study, we validated risk scores for stroke and bleeding in this population and assessed risk of stroke and bleeding among warfarin users compared to nonusers. <b><i>Methods:</i></b> We utilized a cohort of 28,620 pre-dialysis US veterans transitioning to hemodialysis between October 2007 and March 2015. Incident rates for the risks of stroke and bleeding were ascertained based upon CHA₂DS₂-VASc or HAS-BLED scores, respectively. A propensity score-based competing risk analysis was used to assess risk of stroke and bleeding. <b><i>Findings:</i></b> The mean age of our cohort was 77 ± 9 years, and the median CHA₂DS₂-VASc and HAS-BLED scores were 7 (5, 8) and 3 (3, 4), respectively. Increasing CHA₂DS₂-VASc and HAS-BLED scores were predictive of increasing stroke and bleeding rates, respectively. However, warfarin use did not appear to affect the risk of stroke and bleeding (p-interaction = 0.84 for stroke and 0.24 for bleeding). Warfarin use was associated with a higher risk of stroke (adjusted SHR 1.44, 95% CI: 1.23–1.69) and a higher risk of bleeding (adjusted SHR 1.38, 95% CI: 1.25–1.52) when accounting for the competing risk of death. <b><i>Discussion:</i></b> There was no difference in incidence rates of stroke or bleeding among warfarin users versus nonusers. Warfarin was associated with a higher risk of stroke and bleeding after considering mortality risk.

<b><i>引言：</i></b> 抗凝治疗常用于心房颤动（Atrial Fibrillation, AF）患者的卒中预防；然而，接受血液透析（Hemodialysis）的终末期肾病（End-stage Renal Disease, ESRD）患者即便未接受抗凝治疗，出血与卒中的风险也显著升高。目前尚不明确患者在过渡至终末期肾病阶段时，是否应继续接受抗凝治疗。本研究针对该人群验证了卒中与出血风险评分，并对比了华法林（Warfarin）使用者与非使用者的卒中及出血风险。
<b><i>方法：</i></b> 本研究纳入2007年10月至2015年3月期间，28620名由预透析阶段转为接受血液透析的美国退伍军人队列。卒中与出血的发病事件率分别基于CHA₂DS₂-VASc评分（CHA₂DS₂-VASc Score）与HAS-BLED评分（HAS-BLED Score）确定。本研究采用基于倾向得分（Propensity Score）的竞争风险分析（Competing Risk Analysis），评估卒中与出血风险。
<b><i>结果：</i></b> 本队列的平均年龄为77±9岁，CHA₂DS₂-VASc评分与HAS-BLED评分的中位数分别为7（四分位距5~8）与3（四分位距3~4）。CHA₂DS₂-VASc评分升高与卒中风险升高显著相关，HAS-BLED评分升高则与出血风险升高显著相关。然而，华法林使用似乎并未对卒中与出血风险产生独立影响（卒中的交互P值=0.84，出血的交互P值=0.24）。在校正死亡的竞争风险后，华法林使用与更高的卒中风险（校正亚分布风险比（Subdistribution Hazard Ratio, SHR）1.44，95%置信区间（Confidence Interval, CI）1.23~1.69）及更高的出血风险（校正SHR 1.38，95%CI 1.25~1.52）相关。
<b><i>讨论：</i></b> 华法林使用者与非使用者的卒中或出血发病率并无显著差异。在纳入死亡竞争风险进行校正后，华法林与更高的卒中及出血风险相关。