Department of Cardiology, Aalborg University Hospital, 9000 Aalborg, Denmark.
Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg University Hospital, 9260 Gistrup, Denmark.
Eur Heart J Cardiovasc Pharmacother. 2024 Feb 23;10(2):137-146. doi: 10.1093/ehjcvp/pvad091.
Although frail patients with atrial fibrillation (AF) carry a high risk of stroke and treatment-related bleeding complications, evidence for the safety and effectiveness of anticoagulation remains sparse. This study investigated the effectiveness and safety of direct oral anticoagulant (DOAC) vs. warfarin in frail AF patients.
Nationwide registry-based cohort study including 32 048 anticoagulation naïve frail patients (median age 80 years, 53% female) with incident AF during 2012-20. Frailty was assessed using the hospital frailty risk score. To address baseline confounding, we applied inverse probability of treatment weighting (IPTW) and marginal structural models with weighted pooled regression to compute weighted hazard ratios (wHRs) and risk differences for thromboembolism and major bleeding comparing specific DOAC doses with warfarin. After AF diagnosis, 6747 (21.1%) initiated warfarin, 17 076 (50.3%) initiated standard-dose DOAC, and 9179 (28.6%) initiated reduced-dose DOAC. Comparative effectiveness analyses in the IPTW pseudo-populations revealed similar thromboembolism risk between standard-dose DOAC and warfarin [wHR 0.95, 95% confidence interval (CI) 0.80-1.13] and between reduced-dose DOAC and warfarin (wHR 0.97, 95% CI 0.77-1.23). The 1-year thromboembolic event-free survival difference was -0.2% for DOAC, regardless of dosing, vs. warfarin. Major bleeding risk was significantly lower with standard-dose DOAC (wHR 0.69, 95% CI 0.59-0.87) and reduced-dose DOAC (wHR 0.67, 95% CI 0.55-0.81) vs. warfarin. The 1-year bleeding risk difference with DOAC ranged from -1.3% to -3.0%.
Our findings indicate comparable thromboembolism risk and significantly lower bleeding risk with both standard and reduced DOAC regimens compared with warfarin in frail AF patients in routine care.
尽管伴有房颤（AF）的虚弱患者发生卒中及治疗相关出血并发症的风险较高，但抗凝治疗的安全性和有效性证据仍然较少。本研究旨在调查直接口服抗凝剂（DOAC）与华法林在虚弱 AF 患者中的疗效和安全性。
这是一项基于全国注册的队列研究，共纳入 32048 例 2012 年至 20 年期间新诊断为 AF 的、未接受抗凝治疗的虚弱患者（中位年龄 80 岁，53%为女性）。使用医院衰弱风险评分评估衰弱情况。为解决基线混杂问题，我们采用倾向评分逆概率加权（IPTW）和边缘结构模型，对特定 DOAC 剂量与华法林比较计算加权风险比（wHR）和血栓栓塞及大出血风险差异。AF 诊断后，6747 例（21.1%）患者开始使用华法林，17076 例（50.3%）患者开始使用标准剂量 DOAC，9179 例（28.6%）患者开始使用低剂量 DOAC。在 IPTW 拟人群中的比较有效性分析显示，标准剂量 DOAC 和华法林之间的血栓栓塞风险相似[wHR 0.95，95%置信区间（CI）0.80-1.13]，低剂量 DOAC 和华法林之间的血栓栓塞风险也相似[wHR 0.97，95%CI 0.77-1.23]。无论剂量如何，DOAC 与华法林相比，1 年血栓栓塞事件无事件生存率差异为-0.2%。标准剂量 DOAC（wHR 0.69，95%CI 0.59-0.87）和低剂量 DOAC（wHR 0.67，95%CI 0.55-0.81）与华法林相比，大出血风险显著降低。DOAC 与华法林相比，1 年出血风险差异范围为-1.3%至-3.0%。
在常规护理中，与华法林相比，虚弱 AF 患者使用标准剂量和低剂量 DOAC 方案的血栓栓塞风险相当，出血风险显著降低。
