Department of Studies in Public Health, French National Health Insurance (Assurance Maladie/CNAMTS-TS), Paris Cedex 20, France.
Bordeaux Population Health Research Center, Team PHARMACOEPIDEMIOLOGY-UMR 1219, University of Bordeaux, INSERM, Bordeaux, France.
Pharmacotherapy. 2018 Jan;38(1):6-18. doi: 10.1002/phar.2046. Epub 2017 Dec 11.
Direct oral anticoagulants (DOACs) have been proposed as a more convenient alternative to vitamin K antagonists (VKAs), which are commonly associated with poor treatment persistence in non-valvular atrial fibrillation (nv-AF).
Using data from the French national health care databases (Régime Général, 50 million beneficiaries), a cohort study was conducted to compare the 1-year non-persistence rates in nv-AF patients initiating dabigatran (N=11,141) or rivaroxaban (N=11,126) versus VKA (N=11,998). Treatment discontinuation was defined as a switch between oral anticoagulant (OAC) classes or a 60-day gap with no medication coverage, with the additional criterion of no reimbursement for international normalized ratio monitoring during this gap for VKA patients. Considering death as a competing risk, differences between 1-year discontinuation rates were used to compare each DOAC versus VKA. The 95% confidence intervals (CIs) were estimated via bootstrapping. Baseline patient characteristics were adjusted using inverse probability of treatment weighting. Subgroup analyses considered DOAC dose at initiation, age, risk of stroke, and bleeding.
Adjusted 1-year discontinuation rates were higher for dabigatran than for VKA new users (36.8% vs 30.2%; difference: 6.6% [95% CI, 5.5-7.6]) and for rivaroxaban versus VKA new users (33.4% vs 30.4%; 3.0% [1.9-4.1]). Similar differences were found in all subgroup analyses, except in dabigatran and rivaroxaban patients <75 years (dabigatran vs VKA: 0.3% [-1.4 to 1.8]; rivaroxaban vs VKA: -2.6% [-4.3 to -0.9]) and dabigatran 150 mg new users (-1.1% [-3.1 to 0.7]). Consistent results were obtained when considering both switches between OAC classes and death as competing risks of treatment discontinuation.
Results from this nationwide cohort study showed high non-persistence levels with all OACs and suggest that persistence with both dabigatran and rivaroxaban therapy is not better than persistence with VKA therapy. Hospitalizations for bleeding among non-persistent patients were unlikely to explain these high non-persistence rates.
直接口服抗凝剂(DOAC)被提议作为维生素 K 拮抗剂(VKA)的更方便的替代品,VKA 在非瓣膜性心房颤动(nv-AF)中通常与较差的治疗持续性相关。
利用法国国家医疗保健数据库(普通保险,5000 万受益人)的数据,进行了一项队列研究,比较了新开始使用达比加群(N=11141)或利伐沙班(N=11126)与 VKA(N=11998)的 nv-AF 患者的 1 年非持续性率。治疗中断被定义为口服抗凝剂(OAC)类别之间的转换或 60 天无药物覆盖的间隔,对于 VKA 患者,还增加了在这段间隔期间没有 INR 监测报销的额外标准。考虑到死亡是一个竞争风险,使用 1 年停药率的差异来比较每个 DOAC 与 VKA。95%置信区间(CI)通过自举法估计。使用逆概率治疗加权法调整基线患者特征。亚组分析考虑了起始时 DOAC 的剂量、年龄、中风风险和出血风险。
达比加群新使用者的 1 年停药率高于 VKA 新使用者(36.8% vs 30.2%;差异:6.6%[95%CI,5.5-7.6]),利伐沙班新使用者的停药率也高于 VKA 新使用者(33.4% vs 30.4%;3.0%[1.9-4.1])。除了达比加群和利伐沙班<75 岁的患者(达比加群 vs VKA:0.3%[-1.4 至 1.8];利伐沙班 vs VKA:-2.6%[-4.3 至-0.9])和达比加群 150mg 新使用者(-1.1%[-3.1 至 0.7]),所有亚组分析均发现了类似的差异。当同时考虑 OAC 类别的转换和死亡作为治疗中断的竞争风险时,得到了一致的结果。
这项全国性队列研究的结果显示,所有 OAC 的非持续性水平都很高,表明达比加群和利伐沙班治疗的持续性并不优于 VKA 治疗的持续性。非持续性患者的出血住院治疗不太可能解释这些高非持续性率。