Thom Howard H Z, Hollingworth Will, Sofat Reecha, Wang Zhenru, Fang Wei, Bodalia Pritesh N, Bryden Peter A, Davies Philippa A, Caldwell Deborah M, Dias Sofia, Eaton Diane, Higgins Julian P T, Hingorani Aroon D, Lopez-Lopez Jose A, Okoli George N, Richards Alison, Salisbury Chris, Savović Jelena, Stephens-Boal Annya, Sterne Jonathan A C, Welton Nicky J
Bristol Medical School, University of Bristol, Bristol, UK.
University College London, London, UK.
MDM Policy Pract. 2019 Aug 17;4(2):2381468319866828. doi: 10.1177/2381468319866828. eCollection 2019 Jul-Dec.
Determine the optimal, licensed, first-line anticoagulant for prevention of ischemic stroke in patients with non-valvular atrial fibrillation (AF) in England and Wales from the UK National Health Service (NHS) perspective and estimate value to decision making of further research. We developed a cost-effectiveness model to compare warfarin (international normalized ratio target range 2-3) with directly acting (or non-vitamin K antagonist) oral anticoagulants (DOACs) apixaban 5 mg, dabigatran 150 mg, edoxaban 60 mg, and rivaroxaban 20 mg, over 30 years post treatment initiation. In addition to death, the 17-state Markov model included the events stroke, bleed, myocardial infarction, and intracranial hemorrhage. Input parameters were informed by systematic literature reviews and network meta-analysis. Expected value of perfect information (EVPI) and expected value of partial perfect information (EVPPI) were estimated to provide an upper bound on value of further research. At willingness-to-pay threshold £20,000, all DOACs have positive expected incremental net benefit compared to warfarin, suggesting they are likely cost-effective. Apixaban has highest expected incremental net benefit (£7533), followed by dabigatran (£6365), rivaroxaban (£5279), and edoxaban (£5212). There was considerable uncertainty as to the optimal DOAC, with the probability apixaban has highest net benefit only 60%. Total estimated population EVPI was £17.94 million (17.85 million, 18.03 million), with relative effect between apixaban versus dabigatran making the largest contribution with EVPPI of £7.95 million (7.66 million, 8.24 million). At willingness-to-pay threshold £20,000, all DOACs have higher expected net benefit than warfarin but there is considerable uncertainty between the DOACs. Apixaban had the highest expected net benefit and greatest probability of having highest net benefit, but there is considerable uncertainty between DOACs. A head-to-head apixaban versus dabigatran trial may be of value.
从英国国家医疗服务体系（NHS）的角度出发，确定用于预防英格兰和威尔士非瓣膜性心房颤动（AF）患者缺血性卒中的最佳、已获许可的一线抗凝剂，并评估进一步研究对决策的价值。我们建立了一个成本效益模型，以比较华法林（国际标准化比值目标范围为2 - 3）与直接作用（或非维生素K拮抗剂）口服抗凝剂（DOACs）阿哌沙班5毫克、达比加群150毫克、依度沙班6毫克和利伐沙班20毫克在治疗开始后30年的情况。除了死亡，17状态马尔可夫模型还纳入了卒中、出血、心肌梗死和颅内出血等事件。输入参数通过系统文献综述和网络荟萃分析得出。估计了完美信息期望值（EVPI）和部分完美信息期望值（EVPPI），以提供进一步研究价值的上限。在支付意愿阈值为20,000英镑时，与华法林相比，所有DOACs的预期增量净效益均为正值，表明它们可能具有成本效益。阿哌沙班的预期增量净效益最高（7533英镑），其次是达比加群（6365英镑）、利伐沙班（5279英镑）和依度沙班（5212英镑）。关于最佳DOAC存在相当大的不确定性，阿哌沙班净效益最高的概率仅为60%。估计总体人群的EVPI为1794万英镑（1785万，1803万），阿哌沙班与达比加群之间的相对效应在EVPPI中贡献最大，为795万英镑（766万，824万）。在支付意愿阈值为20,000英镑时，所有DOACs的预期净效益均高于华法林，但DOACs之间存在相当大的不确定性。阿哌沙班的预期净效益最高，且净效益最高的概率最大，但DOACs之间存在相当大的不确定性。阿哌沙班与达比加群的直接对比试验可能具有价值。
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