Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, 1225 Center Drive, Gainesville, FL, 32610, USA.
Pharmacoeconomics. 2020 Dec;38(12):1333-1343. doi: 10.1007/s40273-020-00960-0. Epub 2020 Sep 14.
Previous investigations into the cost effectiveness of direct oral anticoagulants only considered individual stroke risk but not bleed risk even though bleeding is an important and potentially fatal side effect for anticoagulated patients.
This study aimed to evaluate the cost effectiveness of dabigatran, rivaroxaban, apixaban, and edoxaban vs warfarin in patients with atrial fibrillation with varying stroke/bleed risk profiles over a lifetime horizon.
A Markov micro-simulation was adapted to examine the lifetime costs and quality-adjusted survival of five anticoagulants from a US private payer's perspective. The study hypothetical cohort consisted of 10,000 patients with atrial fibrillation with age, CHADS-VASc, and HAS-BLED scores similar to a commercially insured patient with atrial fibrillation cohort. Model input parameters including the efficacy and safety of each strategy, utilities, and cost were estimated from public sources, published literature, and analysis conducted in the IBM MarketScan database. Lifetime cost, quality-adjusted life-years, and incremental cost-effectiveness ratios were assessed for each treatment strategy. Subgroup analyses stratified by age, stroke risk score alone, bleed risk score alone and both were performed. Uncertainty was assessed by a deterministic sensitivity analysis and a probabilistic sensitivity analysis.
The base-case analysis suggested dabigatran was the optimal treatment with an incremental cost-effectiveness ratio of $35,055 per quality-adjusted life-year relative to warfarin. Subgroup analyses stratified by age, stroke risk score, and bleed risk score alone were largely consistent with the base-case analysis. Subgroup analyses stratified by both stroke and bleed risk score showed edoxaban was the preferred treatment in patients with a low stroke and a low or medium bleed risk, and patients with a high stroke and low bleed risk. Apixaban was the preferred treatment in patients with a medium stroke and high bleed risk. Results of the deterministic sensitivity analysis indicate the model results were most sensitive to the drug cost and hazard ratio for stroke and bleeding event. Results of the probability sensitivity analysis showed dabigatran is cost effective vs. other treatments in 32.8% and 42.4% of iterations at a willingness to pay of $50,000/quality-adjusted life-year and a willingness to pay of $100,000/quality-adjusted life year, respectively.
From a US private payer's perspective, dabigatran appears cost effective compared with other anticoagulants. This study indicated risk stratification especially considering both stroke and bleed risk simultaneously is important not only in clinical practice but also in health technology assessment exercises among patients with atrial fibrillation.
先前对直接口服抗凝剂的成本效益的研究仅考虑了个体的卒中风险，而没有考虑出血风险，尽管出血是抗凝治疗患者的一个重要且潜在致命的副作用。
本研究旨在评估达比加群、利伐沙班、阿哌沙班和依度沙班相对于华法林在具有不同卒中和出血风险特征的房颤患者中的终生成本效益。
采用马尔可夫微观模拟方法，从美国私人支付者的角度评估 5 种抗凝药物的终生成本和质量调整生存情况。研究假设队列由 10000 名年龄、CHADS-VASc 和 HAS-BLED 评分与商业保险的房颤患者队列相似的房颤患者组成。模型输入参数包括每种策略的疗效和安全性、效用和成本，均来自公共资源、已发表文献和 IBM MarketScan 数据库中的分析。对每种治疗策略的终生成本、质量调整生命年和增量成本效益比进行评估。对年龄、单独的卒中风险评分、单独的出血风险评分以及两者进行分层的亚组分析。通过确定性敏感性分析和概率敏感性分析评估不确定性。
基于案例分析表明，达比加群相对于华法林具有成本效益，增量成本效益比为每质量调整生命年 35055 美元。按年龄、卒中风险评分和单独的出血风险评分进行分层的亚组分析与基于案例的分析基本一致。同时按卒中和出血风险评分分层的亚组分析表明，在低卒中风险和低或中出血风险的患者以及高卒中风险和低出血风险的患者中，依度沙班是首选治疗药物。在具有中卒中和高出血风险的患者中，阿哌沙班是首选治疗药物。确定性敏感性分析的结果表明，模型结果对药物成本和卒中及出血事件的风险比最为敏感。概率敏感性分析的结果表明，达比加群在 50000 美元/质量调整生命年和 100000 美元/质量调整生命年的支付意愿下，相对于其他治疗方法，在 32.8%和 42.4%的迭代中具有成本效益。
从美国私人支付者的角度来看，达比加群相对于其他抗凝剂具有成本效益。本研究表明，风险分层，尤其是同时考虑卒中和出血风险，不仅在临床实践中很重要，在房颤患者的卫生技术评估中也很重要。
