Effectiveness and safety of oral anticoagulants in older adults with non-valvular atrial fibrillation and heart failure

Direct oral anticoagulants (DOACs) are at least as efficacious and safe as warfarin among non-valvular atrial fibrillation (NVAF) patients; limited evidence is available regarding NVAF patients with heart failure (HF). US Medicare enrollees with NVAF and HF initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected. Propensity score matching and Cox models were used to estimate the risk of stroke/systemic embolism (SE), major bleeding (MB), and major adverse cardiac events (MACE) comparing DOACs versus warfarin and DOACs versus DOACs. We identified 10,570 apixaban-warfarin, 4,297 dabigatran-warfarin, 15,712 rivaroxaban-warfarin, 4,263 apixaban-dabigatran, 10,477 apixaban-rivaroxaban, and 4,297 dabigatran-rivaroxaban matched pairs. Compared to warfarin, apixaban had lower rates of stroke/SE (hazard ratio = 0.64, 95% confidence interval = 0.48–0.85), MB (hazard ratio = 0.66, 0.58–0.76), and MACE (hazard ratio = 0.73,0.67–0.79); dabigatran and rivaroxaban had lower rates of MACE (hazard ratio = 0.87,0.77–0.99; hazard ratio = 0.84, 0.79–0.89, respectively). Rivaroxaban had a lower stroke/SE rate (hazard ratio = 0.65, 0.52–0.81) and higher MB rate (hazard ratio = 1.18, 1.08–1.30) versus warfarin. Compared to dabigatran and rivaroxaban, apixaban had lower MB (hazard ratio = 0.71, 0.57–0.89; hazard ratio = 0.55, 0.49–0.63) and MACE rates (hazard ratio = 0.80, 0.69–0.93; hazard ratio = 0.86, 0.79–0.94), respectively. All DOACs had lower MACE rates versus warfarin; differences were observed in stroke/SE and MB. Our findings provide insights about OAC therapy among NVAF patients with HF.

直接口服抗凝药（Direct oral anticoagulants, DOACs）在非瓣膜性心房颤动（non-valvular atrial fibrillation, NVAF）患者中的疗效与安全性至少不劣于华法林，但针对合并心力衰竭（heart failure, HF）的NVAF患者的相关研究证据仍较为有限。本研究纳入美国医保系统中确诊NVAF合并HF且起始使用DOACs（阿哌沙班、利伐沙班、达比加群酯）或华法林的受试者。采用倾向得分匹配与Cox比例风险模型，对比DOACs与华法林、不同DOACs之间的卒中/体循环栓塞（systemic embolism, SE）、大出血（major bleeding, MB）及主要不良心血管事件（major adverse cardiac events, MACE）发生风险。最终匹配得到阿哌沙班-华法林配对10570例、达比加群酯-华法林配对4297例、利伐沙班-华法林配对15712例、阿哌沙班-达比加群酯配对4263例、阿哌沙班-利伐沙班配对10477例、达比加群酯-利伐沙班配对4297例。与华法林相比，阿哌沙班的卒中/SE（风险比=0.64，95%置信区间：0.48~0.85）、MB（风险比=0.66，95%置信区间：0.58~0.76）及MACE（风险比=0.73，95%置信区间：0.67~0.79）发生率均更低；达比加群酯与利伐沙班的MACE发生率更低（风险比分别为0.87，95%置信区间：0.77~0.99；0.84，95%置信区间：0.79~0.89）。与华法林相比，利伐沙班的卒中/SE发生率更低（风险比=0.65，95%置信区间：0.52~0.81），但MB发生率更高（风险比=1.18，95%置信区间：1.08~1.30）。相较于达比加群酯与利伐沙班，阿哌沙班的MB发生率更低（风险比分别为0.71，95%置信区间：0.57~0.89；0.55，95%置信区间：0.49~0.63），MACE发生率亦更低（风险比分别为0.80，95%置信区间：0.69~0.93；0.86，95%置信区间：0.79~0.94）。所有DOACs的MACE发生率均低于华法林，且在卒中/SE与MB方面存在组间差异。本研究结果为合并HF的NVAF患者的口服抗凝药治疗策略提供了临床参考依据。