OBJECTIVE To determine risks of embolic events, bleeding, and mortality with direct oral anticoagulants (DOACs) vs warfarin in people with atrial fibrillation (AF) and dementia. DESIGN New-user retrospective cohort study using The Health Improvement Network database. SETTING AND PARTICIPANTS A population-based sample comprising people with AF and dementia prescribed DOACs or warfarin from August 2011 to September 2017. METHODS Risk of ischemic stroke (IS), ischemic stroke/transient ischemic attack/systemic embolism (IS/TIA/SE), all-cause mortality, intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and other bleeding were compared for DOACs vs warfarin using propensity score-adjusted Poisson regression. Incidence rate ratios (IRRs) and absolute risk differences (ARDs) were calculated. RESULTS Overall, 2399 people with AF and dementia initiated DOACs (42%) or warfarin (58%). Before propensity score adjustment, patients who initiated DOACs were older and had more comorbidities. After adjustment, DOAC initiators demonstrated similar risks of IS, TIA, or SE; IS alone; and other bleeding but reduced ICB risk (IRR 0.27, 95% CI 0.08, 0.86; ARD -5.2, 95% CI -6.5, -1.0, per 1000 person-years) compared with warfarin. Increased risk of GIB (IRR 2.11, 95% CI 1.30, 3.42; ARD 14.8, 95% CI 4.0, 32.4, per 1000 person-years) and all-cause mortality (IRR 2.06, 95% CI 1.60, 2.65; ARD 53.0, 95% CI 30.2, 82.8, per 1000 person-years) were observed in DOAC initiators compared with warfarin. CONCLUSIONS AND IMPLICATIONS Among people with AF and dementia, initiating treatment with DOACs compared with warfarin was associated with similar risks of IS, TIA, or SE and IS alone. DOAC-treated patients demonstrated reduced ICB risk but increased GIB and all-cause mortality risks. We cannot exclude the possible impact of residual confounding from channeling of DOACs toward older and sicker people, particularly for the outcome of all-cause mortality. Further safety data are urgently needed to confirm findings.

中文翻译：

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直接口服抗凝剂与华法林治疗心房颤动和痴呆患者的安全性和有效性

目的 确定房颤 (AF) 和痴呆患者使用直接口服抗凝剂 (DOAC) 与华法林的栓塞事件、出血和死亡风险。使用健康改善网络数据库设计新用户回顾性队列研究。背景和参与者 基于人群的样本，包括 2011 年 8 月至 2017 年 9 月期间服用 DOAC 或华法林的 AF 和痴呆患者。 方法 缺血性中风 (IS)、缺血性中风/短暂性脑缺血发作/全身性栓塞 (IS/TIA/SE) 的风险使用倾向评分调整泊松回归比较 DOAC 与华法林的全因死亡率、颅内出血 (ICB)、胃肠道出血 (GIB) 和其他出血。计算发病率比（IRR）和绝对风险差（ARD）。结果 总体而言，2399 名患有 AF 和痴呆症的患者开始接受 DOAC（42%）或华法林（58%）治疗。在倾向评分调整之前，开始 DOAC 的患者年龄较大且合并症较多。调整后，DOAC发起者表现出类似的IS、TIA或SE风险；是孤独的；与华法林相比，ICB 风险降低（IRR 0.27，95% CI 0.08，0.86；ARD -5.2，95% CI -6.5，-1.0，每 1000 人年）。GIB 风险增加（IRR 2.11，95% CI 1.30, 3.42；ARD 14.8，95% CI 4.0, 32.4，每 1000 人年）和全因死亡率（IRR 2.06，95% CI 1.60, 2.65；ARD 53.0，与华法林相比，DOAC 引发剂的置信区间为 95%（CI 30.2、82.8，每 1000 人年）。结论和意义 在 AF 和痴呆患者中，与华法林相比，开始使用 DOAC 治疗与 IS、TIA 或 SE 和单独 IS 的风险相似。DOAC 治疗的患者表现出 ICB 风险降低，但 GIB 和全因死亡风险增加。我们不能排除 DOAC 对老年人和病情较重的人的影响，尤其是对全因死亡率结果的影响。迫切需要进一步的安全数据来证实研究结果。