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Thromb Haemost 2012; 108(04): 672-682
DOI: 10.1160/TH12-06-0388
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada

Comparative efficacy and cost-effectiveness
Anuraag R. Kansal
1   United BioSource Corporation, Bethesda, Maryland, USA
,
Michael Sharma
2   Division of Neurology University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Carole Bradley-Kennedy
3   Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario, Canada
,
Andreas Clemens
4   Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany
,
Brigitta U. Monz
4   Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany
,
Siyang Peng
1   United BioSource Corporation, Bethesda, Maryland, USA
,
Neil Roskell
5   RTI Health Solutions, Manchester, UK
,
Sonja V. Sorensen
1   United BioSource Corporation, Bethesda, Maryland, USA
› Author Affiliations
Further Information

Publication History

Received: 11 June 2012

Accepted after minor revision: 18 July 2012

Publication Date:
29 November 2017 (online)

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Summary

Canadian patients with atrial fibrillation (AF) in whom anticoagulation is appropriate have two new choices for anticoagulation for prevention of stroke and systemic embolism – dabigatran etexilate (dabigatran) and rivaroxaban. Based on the RE-LY and ROCKET AF trial results, we investigated the cost-effectiveness of dabigatran (twice daily dosing of 150 mg or 110 mg based on patient age) versus rivaroxaban from a Canadian payer perspective. A formal indirect treatment comparison (ITC) of dabigatran versus rivaroxaban was performed, using dabigatran clinical event rates from RE-LY for the safety-on-treatment population, adjusted to the ROCKET AF population. A previously described Markov model was modified to simulate anticoagulation treatment using ITC results as inputs. Model outputs included total costs, event rates, and quality-adjusted life-years (QALYs). The ITC found when compared to rivaroxaban, dabigatran had a lower risk of intracranial haemorrhage (ICH) (relative risk [RR] = 0.38; 95% confidence interval [CI] 0.21 –0.67) and stroke (RR = 0.62; 95%CI 0.45–0.87). Over a lifetime horizon, the model found dabigatran-treated patients experienced fewer ICHs (0.33 dabigatran vs. 0.71 rivaroxaban) and ischaemic strokes (3.40 vs. 3.96) per 100 patient-years, and accrued more QALYs (6.17 vs. 6.01). Dabigatran-treated patients had lower acute care and long-term follow-up costs per patient ($52,314 vs. $53,638) which more than offset differences in drug costs ($7,299 vs. $6,128). In probabilistic analysis, dabigatran had high probability of being the most cost-effective therapy at common thresholds of willingness-to-pay (93% at a $20,000/QALY threshold). This study found dabigatran is economically dominant versus rivaroxaban for prevention of stroke and systemic embolism among Canadian AF patients.

Keywords

Anticoagulation - atrial fibrillation - cost-effectiveness - dabigatran - rivaroxaban - RE-LY - ROCKET AF

 

  • References

  • 1 Gladstone DJ, Bui E, Fang J. et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke 2009; 40: 235-240.
    CrossrefPubMedGoogle Scholar
  • 2 Marini C, De Santis F, Sacco S. et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke 2005; 36: 1115-1119.
    CrossrefPubMedGoogle Scholar
  • 3 Flaherty ML, Tao H, Haverbusch M. et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008; 71: 1084-1089.
    CrossrefPubMedGoogle Scholar
  • 4 Boehringer Ingelheim Canada Ltd. Pradax™ Dabigatran Etexilate capsules product monograph. Available at: http://www.boehringer-ingelheim.ca/en/Home/Human_Health/Our_Products/Product_Monographs/Pradax-pm.pdf. Accessed March 20, 2012.
    PubMedGoogle Scholar
  • 5 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
    CrossrefPubMedGoogle Scholar
  • 6 Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly identified events in the RE-LY trial. N Engl J Med 2010; 363: 1875-1876.
    CrossrefPubMedGoogle Scholar
  • 7 Wann LS, Curtis AB, Ellenbogen KA. et al. 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran) A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Heart Rhythm 2011; 08: e1-8.
    PubMedGoogle Scholar
  • 8 National Institute for Health and Clinical Excellence (NICE). Atrial fibrillation - dabigatran etexilate (TA249). Final Guidance.; March 2012. Available at: http://www.nice.org.uk/ta249. Accessed March 20, 2012.
    PubMedGoogle Scholar
  • 9 Skanes AC, Healey JS, Cairns JA. et al. Focused 2012 update of the canadian cardiovascular society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Canad J Cardiol 2012; 28: 125-136.
    PubMedGoogle Scholar
  • 10 Bayer Inc. XARELTO ™ Rivaroxaban tablet 10 mg, 15 mg and 20 mg antico agulant product monograph. Available at: http://www.bayer.ca/files/XARELTO-PM-ENG-13FEB2012-145763.pdf. Accessed March 20, 2012.
    PubMedGoogle Scholar
  • 11 Patel MR, Mahaffey KW, Garg J. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
    CrossrefPubMedGoogle Scholar
  • 12 Sorensen SV, Kansal AR, Connolly S. et al. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective. Thromb Haemost 2011; 105: 908-919.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Sorensen SV, Dewilde S, Singer DE. et al. Cost-effectiveness of warfarin: trial versus ”real-world“ stroke prevention in atrial fibrillation. Am Heart J 2009; 157: 1064-1073.
    CrossrefPubMedGoogle Scholar
  • 14 Briggs A, Sculpher M. An introduction to Markov modelling for economic evaluation. Pharmacoeconomics 1998; 13: 397-409.
    CrossrefPubMedGoogle Scholar
  • 15 Menon D, Stafinski T. Health technology assessment in Canada: 20 years strong?. Value Health 2009; 12 (Suppl. 02) S14-19.
    CrossrefPubMedGoogle Scholar
  • 16 Fleming TR, Emerson SS. Evaluating rivaroxaban for nonvalvular atrial fibrillation--regulatory considerations. N Engl J Med 2011; 365: 1557-1559.
    CrossrefPubMedGoogle Scholar
  • 17 FDA Advisory Committee Briefing Document - Rivaroxaban. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM270796.pdf. Accessed January 26, 2012.
    PubMed
  • 18 Sullivan PW, Arant TW, Ellis SL. et al. The cost effectiveness of anticoagulation management services for patients with atrial fibrillation and at high risk of stroke in the US. Pharmacoeconomics 2006; 24: 1021-1033.
    CrossrefPubMedGoogle Scholar
  • 19 Tengs TO, Lin TH. A meta-analysis of quality-of-life estimates for stroke. Pharmacoeconomics 2003; 21: 191-200.
    CrossrefPubMedGoogle Scholar
  • 20 Ontario Drug Benefit Program. Drugs Funded by Ontario Drug Benefit (ODB) Program: E-Formulary. 2011 Available at: http://www.health.gov.on.ca/english/providers/program/drugs/odbf_eformulary.html. Accessed March 11, 2011.
    PubMedGoogle Scholar
  • 21 Bayer Health Care. Xarelto 20mg price document. January 17, 2012.
    PubMedGoogle Scholar
  • 22 Canadian Agency for Drugs and Technologies in Health. Guidelines for the economic evaluation of health technologies: Canada [3rd Edition]. Ottawa. 2006
    PubMedGoogle Scholar
  • 23 Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997; 50: 683-691.
    CrossrefPubMedGoogle Scholar
  • 24 Song F, Altman DG, Glenny A M. et al Validit y of in direc t co mpar ison for estimating efficacy of competing interventions: empirical evidence from published metaanalyses. Br Med J 2003; 326: 472.
    CrossrefPubMedGoogle Scholar
  • 25 Canadian Agency for Drugs and Technology in Health. Indirect Evidence: Indirect Treatment Comparisons in Meta-Analysis, March, 2009. Available at: http://www.cadth.ca. Accessed March 21, 2012.
    PubMed
  • 26 FDA Advisory Committee Briefing Document - Dabigatran. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeeting Materials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM247244.pdf. Accessed January 17, 2012.
    PubMed
  • 27 Johnson & Johnson Pharmaceutical Research & Development Advisory Committee Briefing Document Rivaroxaban for the Prevention of Stroke and Non-Central Nervous System (CNS) Systemic Embolism in Patients with Atrial Fibrillation. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM270797.pdf. Accessed January 26, 2012.
    PubMed
  • 28 Jones M, McEwan P, Morgan CL. et al. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart 2005; 91: 472-477.
    CrossrefPubMedGoogle Scholar
  • 29 Canadian Agency for Drugs and Technology in Health. New Oral Anticoagulants for the Prevention of Thromboembolic Events in Patients with Atrial Fibrillation. April 9, 2012. Available at: http://www.cadth.ca/media/pdf/NOAC_Therapeutic_Review_final_report.pdf. Accessed April 20, 2012.
    PubMedGoogle Scholar
  • 30 Lip G, Larsen T, Skjøth F. et al. Indirect Comparisons of New Oral Anticoagulant Drugs for Efficacy and Safety When Used for Stroke Prevention in Atrial Fibrillation. J Am Coll Cardiol. 2012 Epub ahead of print.
    PubMedGoogle Scholar
  • 31 Mantha S, Ansell J. An indirect comparison of dabigatran, rivaroxaban and apixaban for atrial fibrillation. Thromb Haemost 2012; 108: 476-484.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Testa L, Angnifili M, Latini R. et al. Adjusted indirect comparison of new oral anticoagulants for stroke prevention in atrial fibrillation. QJM. 2012 Epub ahead of print.
    PubMedGoogle Scholar
  • 33 Kansal AR, Sorensen SV, Gani R. 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.
    CrossrefPubMedGoogle Scholar
  • 34 Canadian Agency for Drugs and Technology in Health. CEDAC final recommendation: Dabigatran etexilate New indication: Prevention of stroke and systemic embolism in patients with atrial fibrillation. June 22, 2011. Available at: http://www.cadth.ca. Accessed January 16, 2012.
    PubMedGoogle Scholar
  • 35 Kamel H, Johnston SC, Easton JD. et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke 2012; 43: 881-883.
    CrossrefPubMedGoogle Scholar
  • 36 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.
    CrossrefPubMedGoogle Scholar
  • 37 Shah S V, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011; 123: 2562-2570.
    CrossrefPubMedGoogle Scholar
  • 38 Pink J, Lane S, Pirmohamed M. et al. Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefitharm and economic analyses. Br Med J 2011; 343: d6333.
    CrossrefPubMedGoogle Scholar
  • 39 Pengo V, Crippa L, Falanga A. et al. Questions and answers on the use of dabigatran and perspectives 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: 868-876.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Mahaffey KW, Fox KA. Rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. American Heart Association. 2010 Available at: https://www.dtmi.duke.edu/website-administration/files/ROCKET-AF-LBCT-FINAL.ppt/view?searchterm=ROCKET. Accessed April 27, 2012.
    PubMedGoogle Scholar