Department of Pharmacy (C.A.J., L.L.), Veterans Affairs Greater Los Angeles Healthcare System, CA.
Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA (C.A.J).
Circ Cardiovasc Qual Outcomes. 2021 Feb;14(2):e007230. doi: 10.1161/CIRCOUTCOMES.120.007230. Epub 2021 Feb 5.
Patients with heart failure and atrial fibrillation are an important atrial fibrillation subgroup in which direct oral anticoagulants (DOACs) have not been adequately studied in real-world settings. Since DOACs rely on renal elimination and renal dysfunction is prevalent in patients with heart failure, their use may increase bleeding risk, negating some of their advantage over warfarin.
We conducted a retrospective cohort study using linked Veterans Administration databases of patients with heart failure newly started on warfarin or DOACs for atrial fibrillation from October 2010 to August 2017 (23 635 warfarin, 25 823 DOAC). Outcomes included time to first bleeding, stroke, and death using Cox proportional hazards models with inverse probability of treatment weighting.
Total bleeding (hazard ratio, 0.62 [95% CI, 0.56-0.68]), major bleeding (hazard ratio, 0.49 [95% CI, 0.40-0.61]), and death (hazard ratio, 0.74 [95% CI, 0.71-0.78]) were lower with DOAC than warfarin, and with apixaban and dabigatran, but not rivaroxaban. Moderate/severe chronic kidney disease was common (48.7%); moderate chronic kidney disease was associated with increased bleeding with DOACs but not warfarin. However, death and bleeding remained lower with DOACs than warfarin across all renal function levels and clinical subgroups. A >20% transient/persistent decline in renal function occurred in 53% of DOAC-treated patients at some point during follow-up, would have required dose reduction in 10.5% of patients, and was associated with increased bleeding. Dose adjustments were made more often, and bleeding and death were lower in patients seen by pharmacists or anticoagulation clinics. There were significant between-site variations in DOAC dosing.
DOACs overall, apixaban, and dabigatran, but not rivaroxaban, were associated with less total bleeding and death than warfarin in patients with heart failure and atrial fibrillation at all levels of renal function. Renal function decline resulted in increased bleeding in patients with DOACs. DOAC dose adjustment was often indicated, associated with increased bleeding when not adjusted, emphasizing the need for closer monitoring in these patients.
心力衰竭合并心房颤动的患者是心房颤动的一个重要亚组，在真实环境中，直接口服抗凝剂（DOAC）尚未对此类患者进行充分研究。由于 DOAC 依赖于肾脏清除，而心力衰竭患者中肾功能不全较为常见，因此它们的使用可能会增加出血风险，从而抵消其相对于华法林的一些优势。
我们使用退伍军人事务部（VA）数据库进行了一项回顾性队列研究，纳入了 2010 年 10 月至 2017 年 8 月期间新开始使用华法林或 DOAC 治疗心房颤动的心力衰竭患者（华法林 23635 例，DOAC 25823 例）。使用逆概率治疗加权的 Cox 比例风险模型来评估主要出血、卒中和死亡的时间。
与华法林相比，DOAC 可降低总出血风险（风险比，0.62[95%CI，0.56-0.68]）、大出血风险（风险比，0.49[95%CI，0.40-0.61]）和死亡率（风险比，0.74[95%CI，0.71-0.78]），且阿哌沙班和达比加群的结果如此，但利伐沙班并非如此。中度/重度慢性肾脏病较为常见（48.7%）；中度慢性肾脏病与 DOAC 相关的出血风险增加有关，但与华法林无关。然而，在所有肾功能水平和临床亚组中，DOAC 治疗的死亡率和出血率仍低于华法林。在随访期间，53%的 DOAC 治疗患者的肾功能有超过 20%的一过性/持续性下降，10.5%的患者需要调整剂量，并且与出血增加有关。药物剂量调整更频繁，且药师或抗凝门诊患者的出血和死亡率更低。DOAC 的剂量存在显著的站点间差异。
在所有肾功能水平的心力衰竭合并心房颤动患者中，与华法林相比，DOAC 总体上、阿哌沙班和达比加群而非利伐沙班可降低总出血和死亡率。肾功能下降导致 DOAC 治疗患者出血增加。通常需要调整 DOAC 剂量，当未调整剂量时会增加出血风险，这强调了需要对此类患者进行更密切的监测。
