Montero-Balosa Ma Carmen, Limón-Mora Juan A, Leal-Atienza Ana, García-Robredo Beatriz, Sánchez-Villegas Pablo, Isabel-Gómez Rebeca, Aguado-Romeo Ma José, Luque Romero Luis Gabriel, Molina-López Ma Teresa
Primary Care Pharmacy, Aljarafe-Sevilla Norte District. Andalusian Health Service, Seville, Spain.
Coordination of Management and Evaluation, Andalusian Health Service., Seville, Spain.
Front Pharmacol. 2025 Aug 1;16:1548298. doi: 10.3389/fphar.2025.1548298. eCollection 2025.
The aim of this study was to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs: dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin versus acenocoumarol in patients with atrial fibrillation under real-world clinical practice conditions.
This was a retrospective, real-world data-based study. The data source was the Andalusian Population Health Database. The study covered the period from January 2012 to December 2020. Effectiveness outcomes were defined as the identification of a first occurrence of ischaemic or bleeding events, or all-cause mortality. The statistical analysis included crude incidence analysis, survival models: Kaplan-Meier curves, propensity score matched pairs analysis, Fine-Gray model, and Cox regression analysis adjusted for possible confounding.
A total of 150,949 patients were included. The mean age of the cohort was 74 years (48.2% female). The mean follow-up time was 3.3 years. The combined effectiveness endpoint of ischaemic events (transient ischaemic attack, systemic embolism, pulmonary embolism, or ischaemic stroke) showed the following results compared to acenocoumarol: warfarin (RR:1.06; 95%CI 0.93-1.22); dabigatran (RR:1.17; 95%CI 1.02-1.33); rivaroxaban (RR:1.15; 95%CI 1.05-1.26); apixaban (RR: 0.96; 95%CI 0.87-1.07) and edoxaban (RR: 1.10; 95%CI 0.79-1.51). Compared to acenocoumarol, the risk of all-cause mortality was lower for dabigatran, rivaroxaban and apixaban (RR:0.77; 95%CI 0.72-0.82; RR:0.79; 95%CI 0.76-0.83; RR:0.85; 95%CI 0.81-0.89, respectively) and higher for warfarin (RR:1.12; 95%CI 1.05-1.20). An increased risk of gastrointestinal bleeding was observed with dabigatran (RR:1.36; 95%CI 1.09-1.70) and a lower risk with rivaroxaban (RR:0.84; 95%CI 0.72-0.98). All 4 DOACs showed a lower risk of intracranial bleeding compared to acenocoumarol. Warfarin carried a higher risk of both gastrointestinal bleeding (RR:1.64; 95%CI 1.31-2.06) and intracranial bleeding (RR:1.61; 95%CI 1.22-2.13) compared to acenocoumarol. An unadjusted analysis of matched groups in a multivariate Cox regression analysis yielded similar results for combined effectiveness and safety outcomes compared to acenocoumarol.
Although DOACs were clearly associated with a lower risk of intracranial bleeding compared to acenocoumarol, our data did not reveal a significant reduction in thromboembolic events. Warfarin was found to be both less effective and less safe than acenocoumarol.
本研究旨在评估在真实临床实践条件下，直接口服抗凝剂（DOACs：达比加群、利伐沙班、阿哌沙班和依度沙班）及华法林与醋硝香豆素相比，用于心房颤动患者的有效性和安全性。
这是一项基于真实世界数据的回顾性研究。数据来源为安达卢西亚人口健康数据库。研究涵盖2012年1月至2020年12月期间。有效性结局定义为首次发生缺血性或出血性事件，或全因死亡率。统计分析包括粗发病率分析、生存模型：Kaplan-Meier曲线、倾向得分匹配对分析、Fine-Gray模型以及针对可能的混杂因素进行调整的Cox回归分析。
共纳入150,949例患者。队列的平均年龄为74岁（女性占48.2%）。平均随访时间为3.3年。与醋硝香豆素相比，缺血性事件（短暂性脑缺血发作、系统性栓塞、肺栓塞或缺血性卒中）的综合有效性终点显示以下结果：华法林（RR：1.06；95%CI 0.93 - 1.22）；达比加群（RR：1.17；95%CI 1.02 - 1.33）；利伐沙班（RR：1.15；95%CI 1.05 - 1.26）；阿哌沙班（RR：0.96；95%CI 0.87 - 1.07）和依度沙班（RR：1.10；95%CI 0.79 - 1.51）。与醋硝香豆素相比，达比加群、利伐沙班和阿哌沙班的全因死亡率风险较低（RR分别为：0.77；95%CI 0.72 - 0.82；RR：0.79；95%CI 0.76 - 0.83；RR：0.85；95%CI 0.81 - 0.89），而华法林的全因死亡率风险较高（RR：1.12；95%CI 1.05 - 1.20）。观察到达比加群有胃肠道出血风险增加（RR：1.36；95%CI 1.09 - 1.70），利伐沙班有较低风险（RR：0.84；95%CI 0.72 - 0.98）。与醋硝香豆素相比，所有4种DOACs的颅内出血风险均较低。与醋硝香豆素相比，华法林的胃肠道出血（RR：1.64；95%CI 1.31 - 2.06）和颅内出血（RR：1.61；95%CI 1.22 - 2.13）风险均较高。多变量Cox回归分析中匹配组的未调整分析得出，与醋硝香豆素相比，综合有效性和安全性结局的结果相似。
尽管与醋硝香豆素相比，DOACs明显与较低的颅内出血风险相关，但我们的数据并未显示血栓栓塞事件有显著减少。发现华法林的有效性和安全性均低于醋硝香豆素。
