Estimating the cost-effectiveness of treatment for prevention of thromboembolic events in at-risk adults with non-valvular atrial fibrillation
DOI:
https://doi.org/10.7175/fe.v19i1.1346Keywords:
Direct oral anticoagulants, Thromboembolic events, Non-valvular atrial fibrillationAbstract
INTRODUCTION: The direct oral anticoagulants (DOACs) have demonstrated a more predictable effect and a more favorable risk-benefit ratio compared to the standard oral anticoagulant treatment for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF).
AIM: To estimate the efficiency of DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban vs. warfarin), in the prevention of clinical events in adult patients with NVAF.
METHODS: A deterministic incremental cost-effectiveness analysis was performed to evaluate the avoidance of a clinical event and the incremental cost per avoided clinical event, in a hypothetical population of 100,000 adult patients with NVAF, over 1-year period. In the absence of head-to-head comparison trials between DOACs, relative risks were derived from a network meta-analysis. Clinical events considered include stroke/systemic embolism (SE) and major bleeding. Only direct health costs related to the management of clinical events and drug acquisition costs were considered. Clinical event management costs were derived from literature and from the Diagnosis Related Group (DRG) tariffs. Net annual treatment costs were calculated based on the daily dose reported in the Summary of Product Characteristics (SPCs) and the ex-factory price of each drug.
RESULTS: Among DOACs, apixaban was associated with the highest net clinical benefit with 1,064 avoided events over 1 year, compared to warfarin (728 major bleeding events and 336 strokes/SE). Furthermore, apixaban is the most efficient DOAC, with a cost per avoided event equal to € 16,672 vs. warfarin (€ 24,120 for edoxaban 60 mg, € 36,777 for dabigatran 150 mg).
CONCLUSION: Apixaban has the highest potential net clinical benefit among DOACs for patients with NVAF and the least incremental cost per avoided event for the Italian National Health Service.
References
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962; https://doi.org/10.1093/eurheartj/ehw210
Andreotti F, D’Angela D, Mancusi RL, et al. Prevalence of atrial fibrillation, treatment eligibility and consumption of oral anticoagulants in Italian Local Health Authorities: impact of non-vitamin K antagonist oral anticoagulants. G Ital Cardiol 2017; 18: 230-38; https://doi.org/10.1714/2674.27400
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
Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-67; http://dx.doi.org/10.7326/0003-4819-146-12-200706190-00007
Ansell J, Hirsh J, Hylek E, et al.; American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133(6 Suppl): 160S-198S; https://doi.org/10.1378/chest.08-0670
Connolly SJ, Ezekowitz MD, Yusuf S, et al.; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51; http://dx.doi.org/10.1056/NEJMoa0905561
Granger CB, Alexander JH, McMurray JJ, et al.; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-92; http://dx.doi.org/10.1056/NEJMoa1107039
Patel MR, Mahaffey KW, Garg J, et al.; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-91; http://dx.doi.org/10.1056/NEJMoa1009638
Giugliano RP, Ruff CT, Braunwald E, et al.; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093-104; http://dx.doi.org/10.1056/NEJMoa1310907
Biondi-Zoccai G, Malavasi V, D’Ascenzo F, et al. Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses. HSR Proc Intensive Care Cardiovasc Anesth 2013; 5: 40-54
Fu W, Guo H, Guo J, et al. Relative efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation by network meta-analysis. J Cardiovasc Med (Hagerstown) 2014; 15: 873-9; http://dx.doi.org/10.2459/JCM.0000000000000206
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 Technol Assess 2017; 21: 1-386; http://dx.doi.org/10.3310/hta21090
Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955-62; http://dx.doi.org/10.1016/S0140-6736(13)62343-0
Skjøth F, Larsen TB, Rasmussen LH, et al. Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation. An indirect comparison analysis. Thromb Haemost 2014; 111: 981-8; http://dx.doi.org/10.1160/TH14-02-0118
López-López 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 2017; 359: j5058
Diener HC, Aisenberg J, Ansell J, et al. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1. Eur Heart J 2017; 38: 852-859; http://dx.doi.org/10.1093/eurheartj/ehv643
Diener HC, Aisenberg J, Ansell J, et al. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2. Eur Heart J 2017; 38: 860-8; http://dx.doi.org/10.1093/eurheartj/ehw069
Lip GY, Mitchell SA, Liu X, 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; http://dx.doi.org/10.1016/j.ijcard.2015.11.084
Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value Health 2011; 14: 417-28; https://doi.org/10.1016/j.jval.2011.04.002
NICE. Guide to the methods of technology appraisal 2013. Process Published: 4 April 2013 https://www.nice.org.uk/process/pmg9/resources/guide-to-the-methods-of-technology-appraisal-2013-pdf-2007975843781
Tariffe delle prestazioni di assistenza ospedaliera per acuti (sistema DRG). Supplemento ordinario n. 8 alla Gazzetta Ufficiale Serie generale - n. 23 del 28-1-2013
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
OG General Series No. 246 of 22-10-2014. Available at http://www.gazzettaufficiale.it/eli/gu/2014/10/22/246/sg/pdf
OG General Series No. 198 of 25-08-2016. Available at http://www.gazzettaufficiale.it/eli/gu/2016/08/25/198/sg/pdf
Pradelli L, Calandriello M, Di Virgilio R, et al. Comparative pharmacoeconomic assessment of apixaban vs. standard of care for the prevention of stroke in Italian atrial fibrillation patients. Farmeconomia. Health economics and therapeutic pathways 2014; 15(Suppl 1): 15-25; http://dx.doi.org/10.7175/fe.v15i1S.974
Mennini FS, Russo S, Marcellusi A. Budget impact analysis resulting from the use of dabigatran etexilate in preventing stroke in patients with non-valvular atrial fibrillation in Italy. Farmeconomia. Health economics and therapeutic pathways 2012; 13: 121-31; http://dx.doi.org/10.7175/fe.v13i3.268
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 2016; 5: 171-186
Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006; 367: 1903-12
Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009a; 360: 2066-78
Eikelboom JW, Connolly SJ, Hart RG, et al. Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation. J Am Coll Cardiol 2013; 62: 900-8
Renda G, di Nicola M, De Caterina R. Net Clinical Benefit of Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Phase III Atrial Fibrillation Trials. Am J Med 2015; 128: 1007-14; http://dx.doi.org/10.1016/j.amjmed.2015.03.034
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)