Advertisement
Heart, Lung and Circulation

Cost-Effectiveness Analysis of Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Thai Patients With Non-Valvular Atrial Fibrillation

Published:March 20, 2019DOI:https://doi.org/10.1016/j.hlc.2019.02.187

      Background

      Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended as preferred options for stroke prevention in patients with atrial fibrillation (AF) versus warfarin by guidelines worldwide.

      Aim

      This study aimed to evaluate the cost-effectiveness of each NOAC in a Thai health care environment, a country with upper middle-income economies based on the World Bank’s classification.

      Method

      A lifetime Markov model was created from a Thai societal perspective. The model consisted of 19 health states separated into two cycles: event cycle and consequence cycle. The consequences of AF included in the model were ischaemic stroke, intracranial haemorrhage, extracranial haemorrhage, and myocardial infarction. All NOACs available in Thailand (dabigatran 150 mg and 110 mg twice daily; rivaroxaban 20 mg once daily; apixaban 5 mg twice daily; edoxaban 60 mg and 30 mg once daily) were assessed using warfarin with an international normalised ratio of 2–3 as the reference. Inputs were a combination of published literature and local data when available. A willingness-to-pay of 160,000 Thai baht (THB)/quality-adjusted life year (QALY) was used as the threshold of being cost-effective. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were estimated.

      Results

      All NOACs were not cost-effective strategies for the Thai AF population. The ranking of incremental cost-effectiveness ratios from lowest to highest were apixaban 5 mg twice daily (THB 692,136 or US$21,862) followed by edoxaban 60 mg once daily (THB 911,772 or US$28,799), edoxaban 30 mg once daily (THB 913,749 or US$28,861), dabigatran 150 mg twice daily (THB 1,102,106 or US$34,811), dabigatran 110 mg twice daily (THB 1,195,347 or US$37,756), and rivaroxaban 20 mg once daily (THB 1,347,650 or US$42,566). Cost-effectiveness acceptability curve indicated that apixaban had the highest potential to be a cost-effective strategy versus other NOACs.

      Conclusions

      Our findings indicated that all NOACs were not cost-effective in the Thai AF population. Of the NOACs, apixaban may be the most likely to be cost-effective. These data may be useful for policymakers to perform a comprehensive evaluation of these agents for formulary decision and pricing negotiation.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Heart, Lung and Circulation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Chugh S.S.
        • Roth G.A.
        • Gillum R.F.
        • Mensah G.A.
        Global burden of atrial fibrillation in developed and developing nations.
        Glob Heart. 2014; 9: 113-119
        • Chugh S.S.
        • Havmoeller R.
        • Narayanan K.
        • Singh D.
        • Rienstra M.
        • Benjamin E.J.
        • et al.
        Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 study.
        Circulation. 2014; 129: 837-847
        • Odutayo A.
        • Wong C.X.
        • Hsiao A.J.
        • Hopewell S.
        • Altman D.G.
        • Emdin C.A.
        Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis.
        BMJ. 2016; 354: i4482
        • Sithitsook S.
        Thai guideline for diagnosis and treatment of atrial fibrillation.
        Heart Association of Thailand under the Royal Patronage of H.M. the King, Bangkok2012
        • Saokaew S.
        • Sapoo U.
        • Nathisuwan S.
        • Chaiyakunapruk N.
        • Permsuwan U.
        Anticoagulation control of pharmacist-managed collaborative care versus usual care in Thailand.
        Int J Clin Pharm. 2012; 34: 105-112
        • Methavigul K.
        • Boonyapisit W.
        Optimal INR level in Thai atrial fibrillation patients who were receiving warfarin for stroke prevention in Thailand.
        J Med Assoc Thai. 2014; 97: 1274-1280
        • Sterne J.A.
        • Bodalia P.N.
        • Bryden P.A.
        • Davies P.A.
        • Lopez-Lopez J.A.
        • Okoli G.N.
        • et al.
        Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.
        Health Technol Assess. 2017; 21: 1-386
        • Lip G.Y.
        • Mitchell S.A.
        • Liu X.
        • Liu L.Z.
        • Phatak H.
        • Kachroo S.
        • et al.
        Relative efficacy and safety of non-Vitamin K oral anticoagulants for non-valvular atrial fibrillation: network meta-analysis comparing apixaban, dabigatran, rivaroxaban and edoxaban in three patient subgroups.
        Int J Cardiol. 2016; 204: 88-94
        • Jarungsuccess S.
        • Taerakun S.
        Cost-utility analysis of oral anticoagulants for nonvalvular atrial fibrillation patients at the police general hospital, Bangkok, Thailand.
        Clin Ther. 2014; 36: 94 e4
        • Canestaro W.J.
        • Patrick A.R.
        • Avorn J.
        • Ito K.
        • Matlin O.S.
        • Brennan T.A.
        • et al.
        Cost-effectiveness of oral anticoagulants for treatment of atrial fibrillation.
        Circ Cardiovasc Qual Outcomes. 2013; 6: 724-731
        • Harrington A.R.
        • Armstrong E.P.
        • Nolan Jr., P.E.
        • Malone D.C.
        Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation.
        Stroke. 2013; 44: 1676-1681
        • Kansal A.R.
        • Sorensen S.V.
        • Gani R.
        • Robinson P.
        • Pan F.
        • Plumb J.M.
        • et al.
        Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation.
        Heart. 2012; 98: 573-578
        • Bonita R.
        • Beaglehole R.
        Recovery of motor function after stroke.
        Stroke. 1988; 19: 1497-1500
        • Eikelboom J.W.
        • Wallentin L.
        • Connolly S.J.
        • Ezekowitz M.
        • Healey J.S.
        • Oldgren J.
        • et al.
        Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial.
        Circulation. 2011; 123: 2363-2372
        • Granger C.B.
        • Alexander J.H.
        • McMurray J.J.
        • Lopes R.D.
        • Hylek E.M.
        • Hanna M.
        • et al.
        Apixaban versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2011; 365: 981-992
        • Patel M.R.
        • Mahaffey K.W.
        • Garg J.
        • Pan G.
        • Singer D.E.
        • Hacke W.
        • et al.
        Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
        N Engl J Med. 2011; 365: 883-891
        • Giugliano R.P.
        • Ruff C.T.
        • Braunwald E.
        • Murphy S.A.
        • Wiviott S.D.
        • Halperin J.L.
        • et al.
        Edoxaban versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2013; 369: 2093-2104
        • Kongbunkiat K.
        • Kasemsap N.
        • Thepsuthammarat K.
        • Tiamkao S.
        • Sawanyawisuth K.
        National data on stroke outcomes in Thailand.
        J Clin Neurosci. 2015; 22: 493-497
        • Srimahachota S.
        • Boonyaratavej S.
        • Kanjanavanit R.
        • Sritara P.
        • Krittayaphong R.
        • Kunjara-Na-ayudhya R.
        • et al.
        Thai Registry in Acute Coronary Syndrome (TRACS) — an extension of Thai Acute Coronary Syndrome registry (TACS) group: lower in-hospital but still high mortality at one-year.
        J Med Assoc Thai. 2012; 95: 508-518
        • Sangchan A.
        • Sawadpanitch K.
        • Mairiang P.
        • Chunlertrith K.
        • Sukeepaisarnjaroen W.
        • Sutra S.
        • et al.
        Hospitalized incidence and outcomes of upper gastrointestinal bleeding in Thailand.
        J Med Assoc Thai. 2012; 95: S190-S195
        • Strategy and Planning Division Ministry of Public Health
        Public Health Statistics 2014.
        Ministry of Public Health, Nonthaburi, Thailand2015
        • Bank of Thailand
        Rate of exchange of commercial banks.
        Bank of Thailand, Bangkok2018
        • Division of Trade Information and Econoimc Indices Ministry of Commerce
        Consumer price index.
        Ministry of Commerce, Nonthaburi, Thailand2018
        • Permsuwan U.
        • Guntawongwan K.
        • Buddhawongsa P.
        Handling time in economic evaluation studies.
        J Med Assoc Thai. 2014; 97: S50-S58
        • Permsuwan U.
        • Guntawongwan K.
        • Buddhawongsa P.
        Handling time in economic evaluation studies.
        J Med Assoc Thai. 2008; 91: S53-S58
        • Anukoolsawat P.
        • Sritara P.
        • Teerawattananon Y.
        Costs of lifetime treatment of acure coronary syndrome at Ramathibodi hospital.
        Thai Heart J. 2006; 19: 132-143
        • Khiaocharoen O.
        • Pannarunothai S.
        • Zungsontiporn C.
        Cost of acute and sub-acute care for stroke patients.
        J Med Assoc Thai. 2012; 95: 1266-1277
        • Limwattananon S.
        • Limwattananon J.
        • Srisuk P.
        • Sakolchai S.
        Cost-effectiveness analysis of celecoxib on an avoidance of gastrointestianl adverse events in pateints with osteoarthritis.
        Isan J Pharm Sci. 2005; 1: 15-29
        • Archongka Y.
        • Manimmanakorn N.
        • Kuptniratsaikul V.
        • Solunda S.
        • Yee-heng P.
        Unit cost of stroke rehabilitation.
        J Med Assoc Thai. 2008; 91: 1257-1262
        • Santiwongchai B.
        • Kulpeng W.
        • Saphu U.
        • Sukananthachai B.
        • Teerawattananon Y.
        Cost-effectiveness of PT-INR monitoring with point-of-care for dosage adjusment and adverse event in patients receiving warfarin.
        Health Intervention and Technology Assessment Program, Nonthaburi2014
        • Riewpaiboon A.
        Standard cost lists for health economic evaluation in Thailand.
        J Med Assoc Thai. 2014; 97: S127-S134
        • Riewpaiboon A.
        • Riewpaiboon W.
        • Ponsoongnern K.
        • Van den Berg B.
        Economic valuation of informal care in Asia: a case study of care for disabled stroke survivors in Thailand.
        Soc Sci Med. 2009; 69: 648-653
        • National Drug System Development Committee
        Median drug price annoucement.
        Royal Gazette in Thailand, Bangkok2017
        • Berg J.
        • Lindgren P.
        • Nieuwlaat R.
        • Bouin O.
        • Crijns H.
        Factors determining utility measured with the EQ-5D in patients with atrial fibrillation.
        Qual Life Res. 2010; 19: 381-390
        • Haacke C.
        • Althaus A.
        • Spottke A.
        • Siebert U.
        • Back T.
        • Dodel R.
        Long-term outcome after stroke: evaluating health-related quality of life using utility measurements.
        Stroke. 2006; 37: 193-198
        • Hallan S.
        • Asberg A.
        • Indredavik B.
        • Wideroe T.E.
        Quality of life after cerebrovascular stroke: a systematic study of patients’ preferences for different functional outcomes.
        J Intern Med. 1999; 246: 309-316
        • Lacey E.A.
        • Walters S.J.
        Continuing inequality: gender and social class influences on self perceived health after a heart attack.
        J Epidemiol Community Health. 2003; 57: 622-627
        • Lenert L.A.
        • Soetikno R.M.
        Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis.
        J Am Med Inform Assoc. 1997; 4: 49-56
        • Robinson A.
        • Thomson R.
        • Parkin D.
        • Sudlow M.
        • Eccles M.
        How patients with atrial fibrillation value different health outcomes: a standard gamble study.
        J Health Serv Res Policy. 2001; 6: 92-98
        • Sullivan P.W.
        • Ghushchyan V.
        Preference-Based EQ-5D index scores for chronic conditions in the United States.
        Med Decis Making. 2006; 26: 410-420
        • Thavorncharoensap M.
        • Teerawattananon Y.
        • Natanant S.
        • Kulpeng W.
        • Yothasamut J.
        • Werayingyong P.
        Estimating the willingness to pay for a quality-adjusted life year in Thailand: does the context of health gain matter?.
        Clin Outcomes Res. 2013; 5: 29-36
        • Gage B.F.
        • Cardinalli A.B.
        • Albers G.W.
        • Owens D.K.
        Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation.
        JAMA. 1995; 274: 1839-1845
        • Rognoni C.
        • Marchetti M.
        • Quaglini S.
        • Liberato N.L.
        Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis.
        Clin Drug Investig. 2014; 34: 9-17
        • Lip G.Y.
        • Kongnakorn T.
        • Phatak H.
        • Kuznik A.
        • Lanitis T.
        • Liu L.Z.
        • et al.
        Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation.
        Clin Ther. 2014; 36 (e20): 192-210
        • Thavorncharoensap M.
        Measurement of health outcomes.
        J Med Assoc Thai. 2014; 97: S27-S32
        • Chaikledkaew U.
        • Kittrongsiri K.
        Guidelines for health technology assessment in Thailand (second edition) — the development process.
        J Med Assoc Thai. 2014; 97: S4-S9
        • Saokaew S.
        • Permsuwan U.
        • Chaiyakunapruk N.
        • Nathisuwan S.
        • Sukonthasarn A.
        • Jeanpeerapong N.
        Cost-effectiveness of pharmacist-participated warfarin therapy management in Thailand.
        Thromb Res. 2013; 132: 437-443
        • World Health Orgainzation
        Thailand: WHO statistical profile.
        World Health Orgainzation, Geneva2015
        • Gage B.F.
        • Cardinalli A.B.
        • Owens D.K.
        The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life.
        Arch Intern Med. 1996; 156: 1829-1836
        • O’Brien C.L.
        • Gage B.F.
        Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation.
        JAMA. 2005; 293: 699-706