Durand Madeleine, Schnitzer Mireille E, Pang Menglan, Carney Greg, Eltonsy Sherif, Filion Kristian B, Fisher Anat, Jun Min, Kuo I Fan, Renoux Christel, Paterson J Michael, Quail Jacqueline, Matteau Alexis
Internal Medicine Service (Durand), Centre hospitalier de l'Université de Montréal (CHUM) and CHUM Research Centre (Durand); Faculty of Pharmacy (Schnitzer) and Department of Social and Preventive Medicine (Schnitzer), Université de Montréal; Departments of Epidemiology, Biostatistics and Occupational Health (Schnitzer, Pang, Filion, Renoux), Medicine (Filion) and Neurology and Neurosurgery (Renoux), McGill University, Montréal, Que.; Departments of Anesthesiology, Pharmacology and Therapeutics (Carney, Fisher), Faculty of Medicine, University of British Columbia, Vancouver, BC; College of Pharmacy (Eltonsy, Kuo), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Clinical Epidemiology (Filion, Renoux), Lady Davis Institute, Jewish General Hospital, Montréal, Que.; The George Institute for Global Health (Jun), University of New South Wales, Sydney, Australia; ICES Central (Paterson); Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Health Quality Council (Quail) and Department of Community Health and Epidemiology (Quail), University of Saskatchewan, Saskatoon, Sask.; Cardiology Service (Matteau), CHUM and CHUM Research Centre, Montréal, Que.
CMAJ Open. 2020 Dec 18;8(4):E877-E886. doi: 10.9778/cmajo.20200055. Print 2020 Oct-Dec.
Direct oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.
We conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009-2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses.
We included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85).
In this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation.
ClinicalTrials.gov, no. NCT03596502.
在非瓣膜性心房颤动的卒中预防中，直接口服抗凝剂（DOACs）已广泛取代华法林。我们的目的是比较在加拿大环境下，DOACs（达比加群、利伐沙班、阿哌沙班）与华法林在非瓣膜性心房颤动卒中预防方面的安全性和有效性。
我们进行了一项基于人群的观察性多中心队列研究，并进行倾向评分匹配及后续的荟萃分析。我们使用了来自加拿大7个省份（不列颠哥伦比亚省、艾伯塔省、萨斯喀彻温省、马尼托巴省、安大略省、魁北克省和新斯科舍省）的医疗保健数据库。2009年至2017年开始抗凝治疗的非瓣膜性心房颤动患者与开始使用华法林的同等数量患者进行匹配。主要结局是缺血性卒中或全身性栓塞的合并风险比（HR）。次要结局包括大出血的合并HR；卒中、全身性栓塞、大出血和全因死亡率的复合结局；以及心肌梗死。我们使用比例风险Cox回归模型，采用逆概率删失权重法对HR进行建模，并通过随机效应荟萃分析估计合并HR。
我们纳入了128273例开始使用DOACs进行抗凝治疗的患者（40503例使用达比加群，49498例使用利伐沙班，38272例使用阿哌沙班）和128273例开始使用华法林进行抗凝治疗的患者。与华法林相比，DOACs在缺血性卒中或全身性栓塞方面的合并HR为1.02（95%置信区间[CI]为0.87至1.19）。直接口服抗凝剂与较低的大出血发生率（合并HR为0.81，95%CI为0.69至0.97）、复合结局发生率（合并HR为0.81，95%CI为0.74至0.89）和全因死亡率（合并HR为0.81，95%CI为0.78至0.85）相关。
在这项真实世界研究中，与华法林相比，DOACs在缺血性卒中或全身性栓塞方面的风险相似，而在出血和总死亡率方面的风险较低。这些发现支持在非瓣膜性心房颤动中使用DOACs进行抗凝治疗。
ClinicalTrials.gov，编号NCT03596502。
