Comparative pharmacoeconomic assessment of apixaban vs. standard of care for the prevention of stroke in Italian atrial fibrillation patients

Lorenzo Pradelli, Mario Calandriello, Roberto Di Virgilio, Marco Bellone, Marco Tubaro



OBJECTIVES: The aim of this study was to evaluate the cost‑effectiveness of apixaban in the prevention of thromboembolic events in patients with non‑valvular atrial fibrillation (NVAF) relatively to standard of care (warfarin or aspirin) from the Italian National Health System (SSN) perspective.
METHODS: A previously published lifetime Markov model was adapted for Italian context. Clinical effectiveness data were acquired from head‑to‑head randomized trials (ARISTOTLE and AVERROES); main events considered in the model were 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 individual clinical risks and adjusted by utility weights for health states acquired from literature. Unit costs were collected from published Italian sources and actualized to 2013. Costs and health gains accruing 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 (PSA) were carried out to assess the effect of input uncertainty.
RESULTS: Apixaban is expected to reduce the incidence of ischemic events relative to aspirin and to improve bleeding safety profile when compared to warfarin. Incremental LYs (0.31/0.19), QALYs (0.28/0.20), and costs (1,932/1,104) are predicted with the use of apixaban relative to aspirin and warfarin, respectively. The ICERs of apixaban were € 6,794 and € 5,607 per QALY gained, respectively. In PSA, the probability of apixaban being cost effective relative to aspirin and warfarin was 95% and 93%, respectively, for a WTP threshold of € 20,000 per QALY gained. Univariate analyses indicate that results were most sensitive to variations of the absolute risk reduction for cardiovascular events with apixaban.
CONCLUSIONS: Apixaban is expected to increase life expectancy and quality‑adjusted life expectancy, but also costs dedicated to Italian NVAF patients, as compared to standard of care. The resulting ICERs have high probabilities of being below the conventional thresholds of WTP for health benefits of the SSN, indicating efficient allocation of health care resources.


Apixaban; Novel oral anticoagulant agents; Atrial fibrillation

Full Text



  • 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;
  • Kannel WB, Benjamin EJ. Status of the epidemiology of atrial fibrillation. Med Clin North Am 2008; 92: 17-40;
  • 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;
  • 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;
  • 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
  • Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-92;
  • Connolly S, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-17;
  • 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;
  • 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;
  • 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;
  • [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;
  • 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;
  • 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;
  • 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;
  • 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: (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;
  • Brønnum-Hansen H, Davidsen M, Thorvaldsen P. Long-Term Survival and Causes of Death After Stroke. Stroke 2001; 32: 2131-6;
  • 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;
  • 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;
  • 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;
  • Sullivan PW, Slejko JF, Sculpher MJ, et al. Catalogue of EQ-5D scores for the United Kingdom. Med Decis Making 2011; 31: 800-4;
  • 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: (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;
  • Pengo V, Crippa L, Falanga A, et. al; Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation: A consensus document of the Italian Federation of Thrombosis Centers (FCSA). Thromb Haemost 2011; 106: 868-76;
  • 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;
  • 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;
  • 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;
  • 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;


Abstract: 1418 views
HTML: 1234 views
PDF: 246 views


  • There are currently no refbacks.

© SEEd srl