Systematic review of societal costs associated with stroke, bleeding and monitoring in atrial fibrillation
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: Economic consequences associated with the rise in nonvitamin K antagonist oral anticoagulant use on a societal level remain unclear. Materials & methods: Evidence from the past decade on the societal economic burden associated with stroke, bleeding and international normalized ratio monitoring in atrial fibrillation was collected and summarized through a systematic literature review. Results: There were 14 studies identified that reported indirect costs, which were highest among patients with hemorrhagic stroke and intracranial hemorrhage. The contribution of indirect costs to the total was marginal during acute treatment but substantially increased (30–50%) 2 years after stroke and bleeding events. Conclusion: Limited data were available on societal costs in atrial fibrillation and further research is warranted.
Supplementary Material
File (suppl_file.docx)
- Download
- 68.22 KB
References
Papers of special note have been highlighted as: • of interest
1.
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22(8), 983–988 (1991).
2.
Bjorck S, Palaszewski B, Friberg L, Bergfeldt L. Atrial fibrillation, stroke risk, and warfarin therapy revisited: a population-based study. Stroke 44(11), 3103–3108 (2013).
3.
Mcgrath ER, Kapral MK, Fang J et al. Which risk factors are more associated with ischemic stroke than intracerebral hemorrhage in patients with atrial fibrillation? Stroke 43(8), 2048–2054 (2012).
4.
Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: European perspective. Clin. Epidemiol. 6, 213–220 (2014).
5.
Morillo CA, Banerjee A, Perel P, Wood D, Jouven X. Atrial fibrillation: the current epidemic. J. Geriatric Cardiol. 14(3), 195–203 (2017).
6.
Hohnloser SH, Vamos M, Diener HC. [Stroke prevention with direct oral anticoagulants in patients with non-valvular atrial fibrillation]. Dtsch. Med. Wochenschr. 140(10), 750–755 (2015).
7.
Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 361(12), 1139–1151 (2009).
8.
Granger CB, Alexander JH, Mcmurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 365(11), 981–992 (2011).
9.
Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med. 365(10), 883–891 (2011).
10.
Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 369(22), 2093–2104 (2013).
11.
Zirlik A, Bode C. Vitamin K antagonists: relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation. J. Thromb. Thrombolysis 43(3), 365–379 (2017).
12.
Ghatnekar O, Glader EL. The effect of atrial fibrillation on stroke-related inpatient costs in Sweden: a 3-year analysis of registry incidence data from 2001. Value Health 11(5), 862–868 (2008).
13.
Lanitis T, Kongnakorn T, Jacobson L, De Geer A. Cost-effectiveness of apixaban versus warfarin and aspirin in Sweden for stroke prevention in patients with atrial fibrillation. Thrombosis Res. 134(2), 278–287 (2014).
14.
Ntaios G, Papavasileiou V, Makaritsis K, Vemmos K, Michel P, Lip GYH. Real-world setting comparison of nonvitamin-K Antagonist oral anticoagulants versus vitamin-K Antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis. Stroke 48(9), 2494–2503 (2017).
15.
Datamonitor Healthcare. NOACs Pricing, Reimbursement, and Access, ID: 4331629 (2017). https://www.researchandmarkets.com/research/85lxzr/noacs_pricing
16.
Poulsen PB, Johnsen SP, Hansen ML et al. Setting priorities in the health care sector - the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark. Clinicoecon. Outcomes Res. 9, 617–627 (2017).
17.
Pinyol C, Cepeda JM, Roldan I et al. A systematic literature review on the cost-effectiveness of apixaban for stroke prevention in non-valvular atrial fibrillation. Cardiol. Ther. 5(2), 171–186 (2016).
18.
Ferreira J, Mirco A. Systematic review of cost-effectiveness analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation. Rev. Port. Cardiol. 34(3), 179–191 (2015).
19.
Sanders GD, Neumann PJ, Basu A et al. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine. JAMA 316(10), 1093–1103 (2016).
20.
European Network for Health Technology Assessment (Eunethta). Methods for health economic evaluations (2015). https://www.eunethta.eu/wp-content/uploads/2018/03/Methods_for_health_economic_evaluations.pdf
21.
Wolowacz SE, Samuel M, Brennan VK, Jasso-Mosqueda JG, Van Gelder IC. The cost of illness of atrial fibrillation: a systematic review of the recent literature. Europace 13(10), 1375–1385 (2011).
22.
Rolden HJA, Van Der Wilt GJ, Maas A, Grutters JPC. The Gap between economic evaluations and clinical practice: a systematic review of economic evaluations on dabigatran for atrial fibrillation. Int. J. Tech. Assess. Health Care 34(3), 327–336 (2018).
23.
Liberato NL, Marchetti M. Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a systematic and qualitative review. Expert Rev. Pharmacoecon. Outcomes Res. 16(2), 221–235 (2016).
24.
Lopez-Lopez JA, Sterne JaC, Thom HHZ et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ 359, j5058 (2017).
25.
Sterne JA, Bodalia PN, Bryden PA 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 Tech. Assess. 21(9), 1–386 (2017).
26.
Li X, Tse VC, Au-Doung LW, Wong ICK, Chan EW. The impact of ischaemic stroke on atrial fibrillation-related healthcare cost: a systematic review. Europace 19(6), 937–947 (2017).
27.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6(7), e1000097 (2009).
28.
Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration (2011). https://training.cochrane.org/handbook
29.
Garrison LP Jr., Neumann PJ, Erickson P, Marshall D, Mullins CD. Using real-world data for coverage and payment decisions: the ISPOR Real-World Data Task Force report. Value Health 10(5), 326–335 (2007).
30.
Revicki DA, Frank L. Pharmacoeconomic evaluation in the real world. Effectiveness versus efficacy studies. PharmacoEconomics 15(5), 423–434 (1999).
31.
Heidenreich PA, Solis P, Estes NA 3rd et al. 2016 ACC/AHA clinical performance and quality measures for adults with atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J. Am. Coll. Cardiol. 68(5), 525–568 (2016).
32.
Drummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance GW. Methods for the Economic Evaluation of Health Care Programmes. Oxford University Press, Oxford, UK (2015).
33.
Dreyer NA, Schneeweiss S, Mcneil BJ et al. GRACE principles: recognizing high-quality observational studies of comparative effectiveness. Am. J. Manag. Care 16(6), 467–471 (2010).
34.
Ali A, Bailey C, Abdelhafiz AH. Stroke prophylaxis with warfarin or dabigatran for patients with non-valvular atrial fibrillation-cost analysis. Age Ageing 41(5), 681–684 (2012).
35.
Briere JB, Bowrin K, Wood R, Holbrook T, Roberts J. The cost of warfarin treatment for stroke prevention in patients with non-valvular atrial fibrillation in Mexico from a collective perspective. J. Med. Econ. 20(3), 266–272 (2017).
• Retrospective study in Mexico using physician and patient data that provided detailed total, direct and indirect costs associated with international normalized ration monitoring from nonvitamin k antagonists (VKA) treatment. Cost data were broken down by attribution to VKA or not and stratified by worktime loss (employed) and opportunity loss (unemployed).
36.
Briere JB, Bowrin K, Wood R, Roberts J, Tatarsky B. The cost of warfarin treatment for stroke prevention in patients with non-valvular atrial fibrillation in Russia from a collective perspective. J. Med. Econ. 20(6), 599–605 (2017).
• Retrospective study in Russia that provided detailed total, direct and indirect costs associated with international normalized ratio (INR) monitoring from VKA treatment. Cost data were broken down by attribution to vitamin k antagonists or not and stratified by worktime loss (employed) and opportunity loss (unemployed).
37.
Davidson T, Husberg M, Janzon M, Levin LÅ. The cost of thromboembolic events and their prevention among patients with atrial fibrillation. J. Atr. Fibrillation 2(4), 870–880 (2011).
• A Swedish cost-of-illness analysis suggesting that approximately 20% of total lifetime costs per incident stroke case can be attributed to indirect costs.
38.
Ericson L, Bergfeldt L, Bjorholt I. Atrial fibrillation: the cost of illness in Sweden. Eur. J. Health Econ. 12(5), 479–487 (2011).
39.
Hannon N, Daly L, Murphy S et al. Acute hospital, community, and indirect costs of stroke associated with atrial fibrillation: population-based study. Stroke 45(12), 3670–3674 (2014).
• A prospective evaluation of 2-year indirect costs associated with incident and recurring stroke in atrial fibrillation.
40.
Harrington AR, Armstrong EP, Nolan PE Jr, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke 44(6), 1676–1681 (2013).
41.
Jakobsen M, Kolodziejczyk C, Fredslund EK, Poulsen PB, Dybro L, Johnsen SP. Societal costs of first-incident ischemic stroke in patients with atrial fibrillation-A danish nationwide registry study. Value Health 19(4), 413–418 (2016).
• Retrospective Danish registry cost-of-illness study summarizing the direct, indirect and total cost of stroke annually in the incident year of stroke event and the 2 years following the event. The study emphasized the direct cost burden from hospitalization in close proximity to the event and higher indirect cost in subsequent years from productivity losses.
42.
Jarungsuccess S, Taerakun S. Cost-utility analysis of oral anticoagulants for nonvalvular atrial fibrillation patients at the police general hospital, Bangkok, Thailand. Clin. Ther. 36(10), 1389–1394.e1384 (2014).
43.
Jakobsen M, Kolodziejczyk C, Klausen Fredslund E, Poulsen PB, Dybro L, Paaske Johnsen S. Costs of major intracranial, gastrointestinal and other bleeding events in patients with atrial fibrillation - a nationwide cohort study. BMC Health Serv. Res. 17(1), 398 (2017).
• Retrospective Danish registry cost-of-illness study summarizing the direct, indirect and total cost of major bleeding annually in the incident year of bleeding event and the two years following the event. The study emphasized the direct cost burden from hospizalization in close proximity to the event and higher indirect cost in subsequent years from productivity losses and was the only study that reported indirect costs of major bleeding.
44.
Marfatia S, Monz B, Suvarna V, Bhure S, Sangole N. Treatment costs of stroke related to nonvalvular atrial fibrillation patients in India-a multicenter observational study. Value Health Reg. Issues 3(1), 205–210 (2014).
45.
Nguyen E, Egri F, Mearns ES, White CM, Coleman CI. Cost-effectiveness of high-dose edoxaban compared with adjusted-dose warfarin for stroke prevention in non-valvular atrial fibrillation patients. Pharmacotherapy 36(5), 488–495 (2016).
46.
Poulsen PB, Johnsen SP, Hansen ML et al. Setting priorities in the health care sector – the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark. Clinicoecon. Outcomes Res. 9, 617–627 (2017).
47.
Walsh C, Murphy A, Kirby A, Vaughan C. Retrospective costing of warfarin. Irish Med. J. 107(5), 133–135 (2014).
48.
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. Social Sci. Med. 69(4), 648–653 (2009).
49.
Ghatnekar O, Persson U, Glader EL, Terent A. Cost of stroke in Sweden: an incidence estimate. Int. J. Tech. Assess. Health Care 20(3), 375–380 (2004).
50.
Briere JB, Bowrin K, Wood R, Holbrook T, Roberts J. Analysis of the costs associated with vitamin k antagonist treatment for stroke prevention in non valvular atrial fibrialltion in Russia. Presented at: ISPOR 19th Annual European Congress. Vienna, Austria, 29 October–2 November 2016.
51.
Ali A, Bailey C, Abdelhafiz AH. Stroke prophylaxis with warfarin or dabigatran for patients with non-valvular atrial fibrillation-cost analysis. Age Ageing 41(5), 681–684 (2012).
52.
Briere JB, Bowrin K, Wood R, Holbrook T, Roberts J. The cost of warfarin treatment for stroke prevention in patients with non-valvular atrial fibrillation in Mexico from a collective perspective. J. Med. Econ. 20(3), 266–272 (2017).
53.
Jonas DE, Bryant Shilliday B, Laundon WR, Pignone M. Patient time requirements for anticoagulation therapy with warfarin. Med. Decis. Making 30(2), 206–216 (2010).
54.
Svensson P, Andersson S, Ovanfors A, Westlund A. Patient preferenser För olika behandlingsegenskaper Vid antikoagulationsbehandling Hos patienter Med förmaksflimmer Resultat från en svensk multicenter studie. Presented at: Riksstämman, Sweden, 24–26 November 2004.
55.
Danish Health Authorities (Sundhedsstyrelsen). Egenbehandling ved kroniske sygdomme - anbefalinger, der understøtter udbredelse [Treatment of chronic diseases – recommendation that support implementation]. Copenhagen; 2012. Danish (2012). https://www.sst.dk/da/udgivelser/2012/egenbehandling-ved-kroniske-sygdomme---anbefalinger-der-understoetter-udbredelse
56.
Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fbrillation: European perspective. Clin. Epidemiol. 6(1), 213–220 (2014).
57.
Joo H, George MG, Fang J, Wang G. A literature review of indirect costs associated with stroke. J. Stroke Cerebrovasc. Dis. 23(7), 1753–1763 (2014).
58.
Biskupiak J, Ghate SR, Jiao T, Brixner D. Cost implications of formulary decisions on oral anticoagulants in nonvalvular atrial fibrillation. J. Manag. Care Pharm. 19(9), 789–798 (2013).
59.
European Network for Health Technology Assessment (Eunethta). Methods for health economic evaluations (2015). https://www.eunethta.eu/eunethta-methodological-guideline-methods-for-health-economic-evaluations/
Information & Authors
Information
Published In
Pages: 1147 - 1166
PubMed: 31436488
Copyright
© 2019 Bristol-Myers Squibb. This work is licensed under the Creative Commons Attribution 4.0 License
History
Received: 9 July 2019
Accepted: 29 July 2019
Published online: 22 August 2019
Keywords:
Topics
Authors
Metrics & Citations
Metrics
Article Usage
Article usage data only available from February 2023. Historical article usage data, showing the number of article downloads, is available upon request.
Citations
How to Cite
Systematic review of societal costs associated with stroke, bleeding and monitoring in atrial fibrillation. (2019) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2019-0089
Export citation
Select the citation format you wish to export for this article or chapter.
Citing Literature
- Alessandra Buja, Vincenzo Rebba, Laura Montecchio, Giulia Renzo, Vincenzo Baldo, Silvia Cocchio, Nicola Ferri, Federico Migliore, Alessandro Zorzi, Brendan Collins, Cheïma Amrouch, Delphine De Smedt, Christodoulos Kypridemos, Mirko Petrovic, Martin O’Flaherty, Gregory Y.H. Lip, The Cost of Atrial Fibrillation: A Systematic Review, Value in Health, 10.1016/j.jval.2023.12.015, 27, 4, (527-541), (2024).
- Matthew Sussman, Geoffrey D. Barnes, Jennifer D. Guo, Charles Y. Tao, John A. Gillespie, Mauricio Ferri, Nicholas Adair, Matthew S. Cato, Ilnaz Shirkhorshidian, Manuela Di Fusco, The burden of undertreatment and non-treatment among patients with non-valvular atrial fibrillation and elevated stroke risk: a systematic review, Current Medical Research and Opinion, 10.1080/03007995.2021.1982684, 38, 1, (7-18), (2021).
- Konstantinos Vemmos, Nadia Boubouchairopoulou, Panagiotis Stafylas, Elli Vitsou, George Giannakoulas, George Ntaios, Haralampos Milionis, George Hahalis, Frangiskos Parthenakis, Konstantinos Tsioufis, Estimation of the economic burden of atrial fibrillation-related stroke in Greece, Expert Review of Pharmacoeconomics & Outcomes Research, 10.1080/14737167.2021.1979961, 22, 3, (429-435), (2021).
- Stefan Strilciuc, Diana Alecsandra Grad, Constantin Radu, Diana Chira, Adina Stan, Marius Ungureanu, Adrian Gheorghe, Fior-Dafin Muresanu, The economic burden of stroke: a systematic review of cost of illness studies, Journal of Medicine and Life, 10.25122/jml-2021-0361, 14, 5, (606-619), (2021).