Department of Public Health and Clinical Medicine, Umeå University, Sundsvall, Sweden.
Cardiology Department, Sundsvall Hospital, 856 43, Sundsvall, Sweden.
J Thromb Thrombolysis. 2023 Apr;55(3):415-425. doi: 10.1007/s11239-022-02763-w. Epub 2023 Jan 6.
Direct oral anticoagulants (DOACs) used in nonvalvular atrial fibrillation (NVAF) are dose-reduced in elderly and patients with impaired renal function. Only reduced dose dabigatran is concluded as having similar stroke risk reduction and lower risk of major bleeding than warfarin in the pivotal studies. In clinical practice, reduced dose is prescribed more often than expected making this an important issue. The objective of this study was to compare effectiveness and safety between reduced dose DOACs and high TTR warfarin treatment (TTR ≥ 70%) in NVAF. A Swedish anticoagulation registry was used in identifying eligible patients from July 2011 to December 2017. The study cohort consisted of 40,564 patients with newly initiated DOAC (apixaban, dabigatran, or rivaroxaban) (11,083 patients) or warfarin treatment (29,481 patients) after exclusion of 374,135 patients due to not being warfarin or DOAC naïve, not being prescribed reduced dose, having previous mechanical heart valve (MHV), or being under 18 years old. The median durations of follow up were 365, 419, 432 and 473 days for apixaban, dabigatran, rivaroxaban and warfarin, respectively. Warfarin TTR identified from Auricula was 70.0%. Endpoints (stroke and major bleeding) and baseline characteristics were collected from hospital administrative registers using ICD-10 codes. Cohorts were compared using weighted adjusted Cox regression after full optimal matching based on propensity scores. DOACs are associated with lower risk of major bleeding (HR with 95% CI) 0.85 (0.78-0.93), intracranial bleeding HR 0.64 (0.51-0.80), hemorrhagic stroke HR 0.68 (0.50-0.92), gastrointestinal bleeding HR 0.81 (0.69-0.96) and all-cause stroke HR 0.87 (0.76-0.99), than warfarin. Apixaban and dabigatran are associated with lower risk of major bleeding, HR 0.70 (0.63-0.78) and HR 0.80 (0.69-0.94), and rivaroxaban is associated with lower risk of ischemic stroke, HR 0.73 (0.59-0.96), with higher major bleeding risk, HR 1.31 (1.15-1.48), compared to warfarin. Apixaban is associated with higher all-cause mortality compared to warfarin, HR 1.12 (1.03-1.21). DOACs are associated with lower risk of major bleeding and all-cause stroke, than high quality warfarin treatment, with exception of rivaroxaban that carried higher risk of major bleeding and lower risk of stroke or systemic embolism. In this large observational registry-based NVAF cohort, DOACs are preferred treatment in patients with indication for DOAC dose reduction, even in a high TTR setting.
直接口服抗凝剂（DOACs）在非瓣膜性心房颤动（NVAF）中的应用剂量在老年患者和肾功能受损患者中会减少。只有降低剂量的达比加群被认为与关键研究中的华法林相比具有相似的卒中风险降低和大出血风险降低。在临床实践中，降低剂量的处方比预期的更为常见，这是一个重要的问题。本研究的目的是比较 NVAF 中降低剂量的 DOACs 与高 TTR 华法林治疗（TTR≥70%）的有效性和安全性。一项瑞典抗凝登记处被用于从 2011 年 7 月至 2017 年 12 月确定合格患者。研究队列包括 40564 例新开始使用 DOAC（阿哌沙班、达比加群或利伐沙班）的患者（11083 例）或华法林治疗的患者（29481 例），排除了 374135 例由于不是华法林或 DOAC 初治患者、未开降低剂量处方、有既往机械心脏瓣膜（MHV）或年龄在 18 岁以下的患者。阿哌沙班、达比加群、利伐沙班和华法林的中位随访时间分别为 365、419、432 和 473 天。Auricula 识别的华法林 TTR 为 70.0%。终点（卒中和大出血）和基线特征从医院行政登记处使用 ICD-10 代码收集。在基于倾向评分进行完全最优匹配后，使用加权调整的 Cox 回归比较队列。DOACs 与大出血风险降低相关（95%CI 为 HR 0.85[0.78-0.93]）、颅内出血 HR 0.64[0.51-0.80]、出血性卒中 HR 0.68[0.50-0.92]、胃肠道出血 HR 0.81[0.69-0.96]和全因卒中 HR 0.87[0.76-0.99]，与华法林相比。阿哌沙班和达比加群与大出血风险降低相关，HR 0.70[0.63-0.78]和 HR 0.80[0.69-0.94]，利伐沙班与缺血性卒中风险降低相关，HR 0.73[0.59-0.96]，大出血风险增加，HR 1.31[1.15-1.48]，与华法林相比。与华法林相比，阿哌沙班的全因死亡率更高，HR 1.12[1.03-1.21]。DOACs 与大出血和全因卒中风险降低相关，优于高质量华法林治疗，利伐沙班除外，利伐沙班的大出血风险较高，卒中或全身性栓塞风险较低。在这项基于大型观察性登记的 NVAF 队列研究中，DOACs 是具有 DOAC 剂量减少指征的患者的首选治疗方法，即使在 TTR 较高的情况下也是如此。
