Zheng Ying, Sorensen Sonja V, Gonschior Ann-Katrin, Noack Herbert, Heinrich-Nols Jutta, Sunderland Tom, Kansal Anuraag R
Evidera, Bethesda, Maryland.
Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany.
Clin Ther. 2014 Dec 1;36(12):2015-2028.e2. doi: 10.1016/j.clinthera.2014.09.015. Epub 2014 Oct 23.
Three new oral anticoagulants (NOACs) have recently become available in the United Kingdom as an alternative to warfarin in the prevention of stroke and systemic embolism in atrial fibrillation. This study examines the relative cost-effectiveness of dabigatran (BID dosing of 150 mg or 110 mg based on patient age), rivaroxaban, and apixaban from a UK payer perspective.
A previously published model that follows up patients through treatment of atrial fibrillation during a lifetime was adapted to allow comparison of the 3 NOACs and warfarin. Acute thromboembolic and bleeding events, as well as long-term consequences of stroke, intracranial hemorrhage, and acute myocardial infarction, were tracked. Relative efficacy was calculated from a formal indirect treatment comparison using data from the 3 key trials (Randomized Evaluation of Long-Term Anticoagulation Therapy, Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation, and Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) of the NOACs. Data from the rivaroxaban trial were adjusted for the difference in international normalized ratio control among warfarin patients versus the other 2 trials. Model outputs included total costs, event rates, and quality-adjusted life-years.
Among the patients taking NOACs, those taking dabigatran had the highest total QALYs (7.68 QALYs), followed by apixaban (7.63 QALYs) and rivaroxaban (7.47 QALYs). Patients taking dabigatran had the lowest total lifetime costs (£23,342), followed by apixaban (£24,014) and rivaroxaban (£25,220). The differences between dabigatran and apixaban were modest but consistent in sensitivity analyses, with the directionality only changing at the limits of the CIs for the relative risks of ischemic stroke or intracranial hemorrhage or when assuming that both treatment discontinuation and post-event disability rates differ by drug.
Dabigatran was found to be economically dominant over rivaroxaban and apixaban in the UK setting. These economic findings are based on relative clinical efficacy from an indirect treatment comparison and would benefit from any data of direct comparisons of the NOACs in the future.
三种新型口服抗凝剂(NOACs)最近在英国上市,可作为华法林的替代药物,用于预防心房颤动患者的中风和全身性栓塞。本研究从英国医保支付方的角度,考察达比加群(根据患者年龄每日两次给药150mg或110mg)、利伐沙班和阿哌沙班的相对成本效益。
采用一个先前发表的模型,该模型对患者进行终身房颤治疗随访,以比较这三种NOACs和华法林。追踪急性血栓栓塞和出血事件,以及中风、颅内出血和急性心肌梗死的长期后果。使用这三种NOACs的3项关键试验(长期抗凝治疗随机评估、利伐沙班每日一次口服直接Xa因子抑制与维生素K拮抗剂预防心房颤动中风和栓塞试验、阿哌沙班预防心房颤动患者中风试验)的数据,通过正式的间接治疗比较计算相对疗效。对利伐沙班试验的数据进行调整,以反映华法林患者与其他两项试验在国际标准化比值控制方面的差异。模型输出包括总成本、事件发生率和质量调整生命年。
在服用NOACs的患者中,服用达比加群的患者总质量调整生命年最高(7.68个质量调整生命年),其次是阿哌沙班(7.63个质量调整生命年)和利伐沙班(7.47个质量调整生命年)。服用达比加群的患者终身总成本最低(23342英镑),其次是阿哌沙班(24014英镑)和利伐沙班(25220英镑)。在敏感性分析中,达比加群和阿哌沙班之间的差异不大但一致,只有在缺血性中风或颅内出血相对风险的置信区间极限处,或者假设停药和事件后残疾率因药物而异时,方向性才会改变。
在英国的情况下,发现达比加群在经济上优于利伐沙班和阿哌沙班。这些经济研究结果基于间接治疗比较的相对临床疗效,未来若有NOACs直接比较的数据将更有益。