左心耳封堵术、新型口服抗凝药物与华法林预防心房颤动患者卒中风险治疗的成本-效用分析
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摘要
目的对比调整剂量的华法林、新型口服抗凝药物(NOAC)和使用器械Watchman实施的左心耳封堵术(LAAC三种治疗策略在生命周期中预防非瓣膜性心房颤动患者卒中风险的成本-效用分析,为国内医疗保障政策的制定以及临床应用提供依据。方法本文采用回顾性研究方法,从全社会角度出发,基于PROTECT AF等临床试验数据,使用Treeage Pro2011构建Markov模型模拟患者在各治疗策略下30年的成本-效用,评价三种治疗策略在生命周期中预防非瓣膜性心房颤动患者卒中风险的成本-效用,并进行敏感性分析。结果分析结果显示,模型循环120个周期后,调整剂量的华法林组累积的人均成本和效用为37 031.21元和3.202质量调整生命年(QALYs);左心耳封堵术组累积的人均成本和效用为104 989.92元和3.240 QALYs;阿哌沙班组累积的人均成本和效用为105 761.29元和3.234 QALYs;利伐沙班组累积的人均成本和效用为105 645.37元和3.226 QALYs;达比加群酯组累积的人均成本和效用为105 055.04元和3.232 QALYs。与调整剂量的华法林组相比,左心耳封堵术、阿哌沙班、利伐沙班和达比加群酯治疗组的增量成本-效用比分别为1789 705.24元/QALYs、2143 464.55元/QALYs、2882 448.19元/QALYs和2271 355.88元/QALYs。当意愿支付阈值为150 000元/QALYs时,左心耳封堵术和新型口服抗凝药物均不具有成本-效用。敏感性分析显示,脑卒中的年发生率、各药品的日治疗成本、心房颤动状态下患者的效用值、卒中后状态下患者的效用值等对结果影响较大,但各参数在设定的范围内变化不影响模型分析结论。结论从全社会角度出发,在意愿支付阈值为150 000元/QALYs时,与调整剂量的华法林相比,左心耳封堵术和阿哌沙班、利伐沙班及达比加群酯均不具有成本-效用。
Objective The provide basis for the national healthcare policy and clinical application by comparing the cost-utility analysis of three anticoagulation strategies, which include adjusted-dose warfarin, new oral anticoagulation(NOAC), and the left atrial appendage closure(LAAC) by using device Watchman, to prevent stroke risk in patients with non-valvular atrial fibrillation over the life-cycle. Methods By using retrospective research method, based on clinical trials such as PROTECT AF etc., this paper used Treeage Pro 2011 to stimulate the cost-effectiveness of patients under each treatment strategy for 30 years from social perspective, and evelate three treatment strategies in life cycle. The cost effectiveness of prevention of stroke risk in patients with non-valvular atrial fibrillation and sensitivity was analyzed. Results The model showed that the cumulative costs and utilities per patient in adjusted-dose warfarin group were CNY37,031.21 and 3.202 QALYs, CNY 104,989.92 and 3.240 QALYs in LAAC group, CNY 105,761.29 and 3.234 QALYs in apixaban group, CNY 105,645.37 and 3.226 QALYs in rivaroxaban group and CNY 105,055.04 and 3.232 QALYs in dabigatran group. Compared to adjusted-dose warfarin group, the incremental cost utility ratio for LAAC, apixaban, rivaroxaban and dabigatran group were CNY 1,789,705.24/QALYs, CNY 2,143,464.55/QALYs, CNY2,882,448.19/QALYs and CNY 2,271,355.88/QALYs, respectively. When the willingness-to-pay threshold is CNY150,000/QALYs,LAAC, apixaban, rivaroxaban and dabigatran were all no cost-utility. The results from sensitivity analysis showed that the annual incidence of strok, the daily treatment cost of each drug, the utility of patients under atrial fibrillation, the utility of patients after stroke have great influence on the results, but the parameters do not affact the analysis conclusion of the model within the range.Conclusion Compared to adjusted-dose warfarin group, LAAC, apixaban, rivaroxaban and dabigatran group were all no cost-utility.
Objective The provide basis for the national healthcare policy and clinical application by comparing the cost-utility analysis of three anticoagulation strategies, which include adjusted-dose warfarin, new oral anticoagulation(NOAC), and the left atrial appendage closure(LAAC) by using device Watchman, to prevent stroke risk in patients with non-valvular atrial fibrillation over the life-cycle. Methods By using retrospective research method, based on clinical trials such as PROTECT AF etc., this paper used Treeage Pro 2011 to stimulate the cost-effectiveness of patients under each treatment strategy for 30 years from social perspective, and evelate three treatment strategies in life cycle. The cost effectiveness of prevention of stroke risk in patients with non-valvular atrial fibrillation and sensitivity was analyzed. Results The model showed that the cumulative costs and utilities per patient in adjusted-dose warfarin group were CNY37,031.21 and 3.202 QALYs, CNY 104,989.92 and 3.240 QALYs in LAAC group, CNY 105,761.29 and 3.234 QALYs in apixaban group, CNY 105,645.37 and 3.226 QALYs in rivaroxaban group and CNY 105,055.04 and 3.232 QALYs in dabigatran group. Compared to adjusted-dose warfarin group, the incremental cost utility ratio for LAAC, apixaban, rivaroxaban and dabigatran group were CNY 1,789,705.24/QALYs, CNY 2,143,464.55/QALYs, CNY2,882,448.19/QALYs and CNY 2,271,355.88/QALYs, respectively. When the willingness-to-pay threshold is CNY150,000/QALYs,LAAC, apixaban, rivaroxaban and dabigatran were all no cost-utility. The results from sensitivity analysis showed that the annual incidence of strok, the daily treatment cost of each drug, the utility of patients under atrial fibrillation, the utility of patients after stroke have great influence on the results, but the parameters do not affact the analysis conclusion of the model within the range.Conclusion Compared to adjusted-dose warfarin group, LAAC, apixaban, rivaroxaban and dabigatran group were all no cost-utility.
引文
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[2]周自强,胡大一,陈捷,等.中国心房颤动现状的流行病学研究[J].中华内科杂志,2004,43(7):15-18.
[3]Chugh SS,Havmoeller R,Narayanan K,et al.Worldwide Epidemiology of Atrial Fibrillation:a Global Burden of Disease2010 Study[J].Circulation,2014,129(8):837-847
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[6]Hu DY,Sun YH,Zhou ZQ,et al.Risk Factors for Stroke in Chinese with Non Valvular Atrial Fibrillation:a Case Control Study[J].Zhonghua Nei Ke Za Zhi,2003,42(3):157-161.
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[8]Patel MR,Mahaffey KW,Garg J,et al.Rivaroxaban Versus Warfarin in Patients with Atrial Fibrillation[J].N Engl J Med 2011,365(10):883-891.
[9]Connolly SJ,Ezekowitz MD,Yusuf S.Dabigatran Versus Warfarin in Patients with Atrial Fibrillation[J].N Engl J Med,2009,361(12):1139-1151.
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[14]Harrington AR,Armstrong EP,Nolan PE,et al.CostEffectiveness of Apixaban,Dabigatran,Rivaroxaban,and Warfarin for Stroke Prevention in Atrial Fibrillation[J].Stroke,2013,44(6):1676-1681
[15]Lanitis T,CottéFE,Gaudin AF,et al.Stroke Prevention in Patients with Atrial Fibrillation in France:Comparative Cost Effectiveness of New Oral Anticoagulants(Apixaban,Dabigatran,and Rivaroxaban),Warfarin,and Aspirin[J].J Med Econ,2014,17(8):587-598.
[16]Wisloff T,Hagen G,Klemp M.Economic Evaluation of Warfarin,Dabigatran,Rivaroxaban,and Apixaban for Stroke Prevention in Atrial Fibrillation[J].Pharmacoeconomics,2014,32(6):601-612
[17]Liu CY,Chen HC.Cost-Effectiveness Analysis of Apixaban,Dabigatran,Rivaroxaban,and Warfarin for Stroke Prevention in Atrial Fibrillation in Taiwan[J].Clin Drug Investig,2017,37(3):285-293.
[18]Reddy VK,Akehurst RL,Armstrong SO,et al.Time to Cost-Effectiveness Following Stroke Reduction Strategies in AF:Warfarin Versus NOACs Versus LAA Closure[J].J Am Coll Cardiol,2015,66(24):2728-2739.
[19]Lee VW,Tsai RB,Chow IH,et al.Cost-effectiveness Analysis of Left Atrial Appendage Occlusion Compared with Pharmacological Strategies for Stroke Prevention in Atrial Fibrillation[J].BMCCardiovasc Disord,2016,16(1):167.
[20]Reddy VK,Akehurst RL,Amorosi SL,et al.Cost-Effectiveness of Left Atrial Appendage Closure With the WATCHMAN Device Compared With Warfarin or Non-Vitamin K Antagonist Oral Anticoagulants for Secondary Prevention in Nonvalvular Atrial Fibrillation[J].Stroke,2018,49(6):1464-1470
[21]陈永法,韩洪娜.达比加群和利伐沙班及华法林预防心房颤动并发脑卒中的经济学评价[J].中国新药杂志,2016,25(11):1216-1224.
[22]吴玥,冯静,彭燕,等.阿哌沙班与华法林用于非瓣膜性房颤患者卒中防治的成本效果分析[J].中国现代应用药学,2016,33(9):1183-1188.
[23]朱水清,张明东,曾治宇,等.左心耳封堵术对比华法林预防心房颤动患者血栓栓塞的卫生经济学评价[J].中国药物经济学,2017,12(11):5-9.
[24]WHO.Choosing Interventions that are Cost Effective(WHO-CHOICE),Threshold Values for Intervention Cost-Effectiveness by Region[S/OL].2010[2016-01-29].http://www.who.int/choice/costs/CER_levels/en/.
[25]胡善联,杨莉,陈慧云.药物经济学评价指南研究[M].复旦大学出版社,2004.
[26]陈军,钟镝,李国忠.卒中评分量表新进展[J].神经疾病与精神卫生,2012,12(3):322-324.
[27]中华人民共和国国家卫生和计划生育委员会.2011中国卫生统计年鉴[R].北京,2013.
[28]《老年人心房颤动诊治中国专家建议》写作组,中华医学会老年医学分会,《中华老年医学杂志》编辑委员会.老年人心房颤动诊治中国专家建议[J].中华老年医学杂志,2011,30(11):894-908.
[29]Sullivan PW,Lawrence WF,Ghushchyan V.A National Catalog of Preference-based Scores for Chronic Conditions in the United States[J].Med Care,2005,43(7):736-749.
[30]Sullivan PW,Aranttw,Ellissl,et al.The Cost Effectiveness of Anticoagulation Management Services for Patients with Atrial Fibrillation and at High Risk of Stroke in the US[J].Pharmacoeconomics,2006,24(10):1021-1033.
[31]Gage BF,Cardinalli AB,Owens DK.The Effect of Stroke and Stroke Prophylaxis with Aspirin or Warfarin on Quality of Life[J].Arch Intern Med,1996,156(16):1829-1836.
[32]Freeman JV,Zhu RP,Owens DK,et al.Cost-effectiveness of Dabigatran Compared with Warfarin for Stroke Prevention in Atrial Fibrillation[J].Ann Intern Med,2011,154(1):1-11.
[2]周自强,胡大一,陈捷,等.中国心房颤动现状的流行病学研究[J].中华内科杂志,2004,43(7):15-18.
[3]Chugh SS,Havmoeller R,Narayanan K,et al.Worldwide Epidemiology of Atrial Fibrillation:a Global Burden of Disease2010 Study[J].Circulation,2014,129(8):837-847
[4]Krijthe BP,Kunst A,Benjamin EJ,et al.Projections on the Number of Individuals with Atrial Fibrillation in the European Union,from 2000 to 2060[J].Eur Heart J,2013,34(35):2746-2751
[5]Hijazi Z,Oldgren J,Andersson U,et al.Cardiac Biomarkers are Associated with an Increased Risk of Stroke and Death in Patients with Atrial Fibrillation:a Randomized Evaluation of Long-term Anticoagulation Therapy(RE-LY)Sub Study[J].Circulation,2012,125(13):1605-1616.
[6]Hu DY,Sun YH,Zhou ZQ,et al.Risk Factors for Stroke in Chinese with Non Valvular Atrial Fibrillation:a Case Control Study[J].Zhonghua Nei Ke Za Zhi,2003,42(3):157-161.
[7]European Heart Rhythm Association,European Association for Cardio-Thoracic Surgery,Camm AJ,et al.Guidelines for the Management of Atrial Fibrillation:the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology(ESC)[J].Eur Heart J,2010,31(19):2369-2429.
[8]Patel MR,Mahaffey KW,Garg J,et al.Rivaroxaban Versus Warfarin in Patients with Atrial Fibrillation[J].N Engl J Med 2011,365(10):883-891.
[9]Connolly SJ,Ezekowitz MD,Yusuf S.Dabigatran Versus Warfarin in Patients with Atrial Fibrillation[J].N Engl J Med,2009,361(12):1139-1151.
[10]Granger CB,Alexander JH,Mcmurray JJ,et al.Apixaban Versus Warfarin in Patients with Atrial Fibrillation[J].N Engl JMed,2011,365(11):981-992
[11]Holmes DR,Reddy VY,Turi ZG,et al.Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients with Atrial Fibrillation:a Randomized Non-inferiority Trial[J].Lancet 2009,374(9689):534-542.
[12]Holmes DR Jr,Kar S,Price MJ,et al.Prospective Randomized Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients with Atrial Fibrillation Versus Long-term Warfarin Therapy:the PREVAIL Trial[J].J Am Coll Cardiol,2014,64(1):1-12.
[13]Reddy VY,Mobius-Winkler S,Miller MA,et al.Left Atrial Appendage Closure with the Watchman Device in Patients with a Contraindication for Oral Anticoagulation:the ASAP Study(ASAPlavix Feasibility Study with Watchman Left Atrial Appendage Closure Technology)[J].J Am Coll Cardiol,2013,61(25):2551-2556.
[14]Harrington AR,Armstrong EP,Nolan PE,et al.CostEffectiveness of Apixaban,Dabigatran,Rivaroxaban,and Warfarin for Stroke Prevention in Atrial Fibrillation[J].Stroke,2013,44(6):1676-1681
[15]Lanitis T,CottéFE,Gaudin AF,et al.Stroke Prevention in Patients with Atrial Fibrillation in France:Comparative Cost Effectiveness of New Oral Anticoagulants(Apixaban,Dabigatran,and Rivaroxaban),Warfarin,and Aspirin[J].J Med Econ,2014,17(8):587-598.
[16]Wisloff T,Hagen G,Klemp M.Economic Evaluation of Warfarin,Dabigatran,Rivaroxaban,and Apixaban for Stroke Prevention in Atrial Fibrillation[J].Pharmacoeconomics,2014,32(6):601-612
[17]Liu CY,Chen HC.Cost-Effectiveness Analysis of Apixaban,Dabigatran,Rivaroxaban,and Warfarin for Stroke Prevention in Atrial Fibrillation in Taiwan[J].Clin Drug Investig,2017,37(3):285-293.
[18]Reddy VK,Akehurst RL,Armstrong SO,et al.Time to Cost-Effectiveness Following Stroke Reduction Strategies in AF:Warfarin Versus NOACs Versus LAA Closure[J].J Am Coll Cardiol,2015,66(24):2728-2739.
[19]Lee VW,Tsai RB,Chow IH,et al.Cost-effectiveness Analysis of Left Atrial Appendage Occlusion Compared with Pharmacological Strategies for Stroke Prevention in Atrial Fibrillation[J].BMCCardiovasc Disord,2016,16(1):167.
[20]Reddy VK,Akehurst RL,Amorosi SL,et al.Cost-Effectiveness of Left Atrial Appendage Closure With the WATCHMAN Device Compared With Warfarin or Non-Vitamin K Antagonist Oral Anticoagulants for Secondary Prevention in Nonvalvular Atrial Fibrillation[J].Stroke,2018,49(6):1464-1470
[21]陈永法,韩洪娜.达比加群和利伐沙班及华法林预防心房颤动并发脑卒中的经济学评价[J].中国新药杂志,2016,25(11):1216-1224.
[22]吴玥,冯静,彭燕,等.阿哌沙班与华法林用于非瓣膜性房颤患者卒中防治的成本效果分析[J].中国现代应用药学,2016,33(9):1183-1188.
[23]朱水清,张明东,曾治宇,等.左心耳封堵术对比华法林预防心房颤动患者血栓栓塞的卫生经济学评价[J].中国药物经济学,2017,12(11):5-9.
[24]WHO.Choosing Interventions that are Cost Effective(WHO-CHOICE),Threshold Values for Intervention Cost-Effectiveness by Region[S/OL].2010[2016-01-29].http://www.who.int/choice/costs/CER_levels/en/.
[25]胡善联,杨莉,陈慧云.药物经济学评价指南研究[M].复旦大学出版社,2004.
[26]陈军,钟镝,李国忠.卒中评分量表新进展[J].神经疾病与精神卫生,2012,12(3):322-324.
[27]中华人民共和国国家卫生和计划生育委员会.2011中国卫生统计年鉴[R].北京,2013.
[28]《老年人心房颤动诊治中国专家建议》写作组,中华医学会老年医学分会,《中华老年医学杂志》编辑委员会.老年人心房颤动诊治中国专家建议[J].中华老年医学杂志,2011,30(11):894-908.
[29]Sullivan PW,Lawrence WF,Ghushchyan V.A National Catalog of Preference-based Scores for Chronic Conditions in the United States[J].Med Care,2005,43(7):736-749.
[30]Sullivan PW,Aranttw,Ellissl,et al.The Cost Effectiveness of Anticoagulation Management Services for Patients with Atrial Fibrillation and at High Risk of Stroke in the US[J].Pharmacoeconomics,2006,24(10):1021-1033.
[31]Gage BF,Cardinalli AB,Owens DK.The Effect of Stroke and Stroke Prophylaxis with Aspirin or Warfarin on Quality of Life[J].Arch Intern Med,1996,156(16):1829-1836.
[32]Freeman JV,Zhu RP,Owens DK,et al.Cost-effectiveness of Dabigatran Compared with Warfarin for Stroke Prevention in Atrial Fibrillation[J].Ann Intern Med,2011,154(1):1-11.