University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool Centre for Cardiovascular Science, Liverpool L69 3BX, UK.
Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Fredrik Bajers Vej 7K, 9220 Aalborg Øst, Denmark.
Eur Heart J Cardiovasc Pharmacother. 2021 Sep 21;7(5):405-414. doi: 10.1093/ehjcvp/pvaa117.
Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs).
A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01 January 2013 to 30 September 2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥6 concomitant medications on the index date. Propensity score matching was conducted to compare non-vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188 893 patients with polypharmacy were included, with an average of 8 concomitant medications (interquartile range 6-9). Compared to warfarin, apixaban [hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.52-0.68], and rivaroxaban (HR: 0.75, 95% CI: 0.69-0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54-0.61) and dabigatran (HR: 0.76, 95% CI: 0.66-0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban.
In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favourable for NOACs vs. warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.
非瓣膜性心房颤动（NVAF）患者普遍存在多种药物治疗，这对 NVAF 的有效管理提出了潜在问题。本研究比较了新开始使用口服抗凝剂（OAC）的多种药物治疗 NVAF 患者发生卒中/系统性栓塞（SE）和大出血（MB）的风险。
本研究采用美国 CMS 医疗保险和四个商业数据库，对 2013 年 1 月 1 日至 2015 年 9 月 30 日期间开始使用 OAC 的多种药物治疗 NVAF 患者进行了回顾性研究。在索引日期时，同时使用≥6 种伴随药物定义为多种药物治疗。采用倾向评分匹配比较非维生素 K 拮抗剂 OAC（NOAC）与华法林以及 NOAC 之间的差异。采用 Cox 比例风险模型评估卒中/SE 和 MB 的风险。共纳入 188893 例多种药物治疗的患者，平均同时使用 8 种伴随药物（四分位间距 6-9）。与华法林相比，阿哌沙班（HR：0.59，95%CI：0.52-0.68）和利伐沙班（HR：0.75，95%CI：0.69-0.83）与卒中/SE 风险降低相关。与华法林相比，阿哌沙班（HR：0.57，95%CI：0.54-0.61）和达比加群（HR：0.76，95%CI：0.66-0.88）与 MB 风险降低相关。与达比加群和利伐沙班相比，阿哌沙班与较低的卒中/SE 和 MB 风险相关。与利伐沙班相比，达比加群与较低的 MB 风险相关。
在这项针对多种药物治疗 NVAF 患者的抗凝治疗观察性研究中，NOAC 与华法林相比，有效性和安全性更具优势。我们的观察结果是假设性的，可能有助于为未来的临床试验提供信息，以指导在多种药物治疗患者中选择合适的 OAC 治疗。
