Cost‑effectiveness analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients
DOI:
https://doi.org/10.7175/fe.v15i4.971Keywords:
Apixaban, Novel oral anticoagulant agents, Atrial fibrillationAbstract
OBJECTIVES: The study evaluated the cost‑effectiveness of apixaban in preventing thromboembolic events in non‑valvular atrial fibrillation (NVAF) patients, as compared to other three available novel oral anticoagulant agents (NOACs), from the Italian Health System (SSN) perspective.
METHODS: A previously published lifetime Markov model was adapted for the Italian context. Baseline clinical risks were assigned based on the demographic and clinical features of the patients; effectiveness and safety parameters derived from adjusted indirect comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Expected survival was projected beyond trial duration using national mortality data adjusted for clinical risks and weighted by published utilities. Unit costs were collected from published Italian sources and actualized to 2013. Costs and health gains occurring after the first year were discounted at an annual 3.5% rate. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio (ICER), where effectiveness is measured in terms of life‑years and quality adjusted life‑years gained. Deterministic and probabilistic sensitivity analyses (DSA&PSA) were carried out.
RESULTS: In the short to medium term, apixaban was associated with marginal LYs and QALYs gains and slight savings, as compared to other NOACs. However, as apixaban extended expected survival versus dabigatran (110mg), dabigatran (150mg) and rivaroxaban (0.13, 0.08, and 0.06 LYs or 0.11, 0.07, and 0.05 QALYs), expected total lifetime costs exceeded those of these comparators (€ 319, € 282, and € 16). Corresponding ICERs were estimated in € 2,911, € 3,882 and € 327 per QALY gained. The most influential parameter according to DSA was daily costs of NOACs, but the corresponding ICERs remained well below commonly accepted WTP values. In PSA, the probabilities of apixaban being cost effective with a WTP threshold of 20,000 €/QALY gained were 99%, 92% and 93% for the same comparisons.
CONCLUSIONS: Apixaban is expected to be more effective than dabigatran and rivaroxaban in Italian NVAF population, and marginally more costly due to consume healthcare resources for a longer period of time. The ICERs have a high likelihood of being below conventional thresholds of WTP for health benefits of the SSN and suggest that apixaban is cost‑effective compared with other three available NOACs.
References
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). Eur Heart J 2010; 31: 2369-429; http://dx.doi.org/10.1093/eurheartj/ehq278
Kannel WB, Benjamin EJ. Status of the epidemiology of atrial fibrillation. Med Clin North Am 2008; 92: 17-40; http://dx.doi.org/10.1016/j.mcna.2007.09.002
Wolf CD, Rudd AG. The Burden of Stroke White paper: Raising awareness of the global toll of stroke-related disability and death
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-8; http://dx.doi.org/10.1161/01.STR.22.8.983
Lamassa M, Di Carlo A, Pracucci G, et al. Characteristics, outcome, and care of stroke associated with atrial fibrillation in Europe: data from a multicenter multinational hospital-based registry (The European Community Stroke Project). Stroke 2001; 32: 392-8; http://dx.doi.org/10.1161/01.STR.32.2.392
Sacchetti MA, Spandonaro F, Finzi G, et al. Prevenzione dell’ictus in Italia – diversità regionali ed assetti. Sole 24 Ore sanità Allegato al n.10 del 15-21 Marzo 2011
National Institute for Health and Care Excellence. Atrial fibrillation: the management of atrial fibrillation. NICE Clinical guideline 36. NHS, 2006
Summary of Product Characteristics [SPC] of apixaban
AIFA. Piano Terapeutico Eliquis® (apixaban)
Dorian P, Kongnakorn T, Phatak H, et al. Cost-effectiveness of apixaban vs. current standard of care for stroke prevention in patients with atrial Fibrillation. Eur Heart J 2014; 35: 1897-906; http://dx.doi.org/10.1093/eurheartj/ehu006
Lip GYH, Kongnakorn T, Phatak H, et al. Cost-Effectiveness of Apixaban Versus Other New Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation. Clin Ther 2014; 36: 192-210; http://dx.doi.org/10.1016/j.clinthera.2013.12.011
Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-92; http://dx.doi.org/10.1056/NEJMoa1107039
Olesen JB, Lip GY, Hansen ML, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011; 342: d124; http://dx.doi.org/10.1136/bmj.d124
Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51; http://dx.doi.org/10.1056/NEJMoa0905561
Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-91; http://dx.doi.org/10.1056/NEJMoa1009638
[No author listed]. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154: 1449-57; http://dx.doi.org/10.1001/archinte.1994.00420130036007
Ariesen M, Claus S, Rinkel G, et al. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke 2003; 34: 2060-5; http://dx.doi.org/10.1161/01.STR.0000080678.09344.8D
Mohan KM, Crichton SL, Grieve AP, et al. Frequency and predictors for the risk of stroke recurrence up to 10 years after stroke: the South London Stroke Register. J Neurol Neurosurg Psychiatry 2009; 80: 1012-8; http://dx.doi.org/10.1136/jnnp.2008.170456
Connolly S, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-17; http://dx.doi.org/10.1056/NEJMoa1007432
Freeman JV, Zhu RP, Owens DK, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med 2011; 154: 1-11; http://dx.doi.org/10.7326/0003-4819-154-1-201101040-00289
Scarborough P, Bhatnagar P. Coronary Heart Disease statistics 2010 edition; British Health Foundation Health Promotion research group, Department of Public Health, University of Oxford
ISTAT. Available at: www.ISTAT.it (last accessed February 2014)
Friberg L, Hammar N, Pettersson H, et al. Increased mortality in paroxysmal atrial fibrillation: report from the Stockholm Cohort-Study of Atrial Fibrillation (SCAF). Eur Heart J 2007; 28: 2346-53; http://dx.doi.org/10.1093/eurheartj/ehm308
Brønnum-Hansen H, Davidsen M, Thorvaldsen P. Long-Term Survival and Causes of Death After Stroke. Stroke 2001; 32: 2131-6; http://dx.doi.org/10.1161/hs0901.094253
Henriksson K, Farahmand B, Johansson S, et al. Survival after stroke - The impact of CHADS2 score and AF. Int J Cardiol 2010; 141: 18-23; http://dx.doi.org/10.1016/j.ijcard.2008.11.122
Huybrechts K, Caro J, Xenakis J. The prognostic value of the modified rankin scale score for long-term survival after first-ever stroke. Cerebrovasc Dis 2008; 26: 381-7; http://dx.doi.org/10.1159/000151678
Brønnum-Hansen H, Jorgensen T, Davidsen M, et al. Survival and cause of death after myocardial infarction: the Danish MONICA study. J Clin Epidemiol 2001; 54: 1244-50; http://dx.doi.org/10.1016/S0895-4356(01)00405-X
Sullivan P, Slejko J, Sculpher M, et al. Catalogue of EQ-5D scores for the United Kingdom. Med Decis Making 2011; 31: 800-4; http://dx.doi.org/10.1177/0272989X11401031
Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med 1996; 156: 1829-36
Informatore Farmaceutico on-line. Available at: http://www.codifa.it/ (last accessed February 2014)
Lucioni C, Garancini MP, Massi-Benedetti M, et al. The costs of type 2 diabetes mellitus in Italy: a CODE-2 sub-study. Treat Endocrinol 2003; 2: 121-33; http://dx.doi.org/10.2165/00024677-200302020-00005
Fattore G, Torbica A, Susi A, et al. The social and economic burden of stroke survivors in Italy: a prospective, incidence-based, multi-centre cost of illness study. BMC Neurology 2012; 12: 137; http://dx.doi.org/10.1186/1471-2377-12-137
Remunerazione prestazioni di assistenza ospedaliera per acuti, assistenza ospedaliera di riabilitazione e di lungodegenza post acuzie e di assistenza specialistica ambulatoriale. DM 10/2012 on Gazzetta Ufficiale n. 23 of 1/28/2013
Mantovani LG, Fornari C, Madotto F, et al. Burden of acute myocardial infarction. Int J Cardiol 2011; 150: 111-2; http://dx.doi.org/10.1016/j.ijcard.2011.04.030
Colombo GL, Caruggi M, Vinci M, et al. Costo sociale annuo della dispepsia funzionale dopo l’eradicazione dell’Helicobacter pylori. PharmacoEconomics – Italian Research Articles 2005; 7: 27-42; http://dx.doi.org/10.1007/BF03320533
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. The Publication Agreement can be downloaded here, and should be signed by the Authors and sent to the Publisher when the article has been accepted for publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).
- Authors are permitted to post their work online after publication (the article must link to publisher version, in html format)