Thromb Haemost 2011; 105(05): 908-919
DOI: 10.1160/TH11-02-0089
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: A Canadian payer perspective

Sonja V. Sorensen
1   United BioSource Corporation, Bethesda, Maryland, USA
,
Anuraag R. Kansal
1   United BioSource Corporation, Bethesda, Maryland, USA
,
Stuart Connolly
2   Population Health Research Institute, Hamilton, Ontario, Canada
,
Siyang Peng
1   United BioSource Corporation, Bethesda, Maryland, USA
,
John Linnehan
1   United BioSource Corporation, Bethesda, Maryland, USA
,
Carole Bradley-Kennedy
3   Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario, Canada
,
Jonathan M. Plumb
4   Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany
› Author Affiliations
Financial support:The project was funded by Boehringer Ingelheim Canada Ltd (BI).
Further Information

Publication History

Received: 09 February 2011

Accepted after minor revision: 14 March 2011

Publication Date:
28 November 2017 (online)

Summary

Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in whom anticoagulation is appropriate. Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing (150 mg bid for patients <80 years, 110 mg bid for patients ≥80 years) versus warfarin and “real-world” prescribing (i.e. warfarin, aspirin, or no treatment in a cohort of warfarin-eligible patients) from a Canadian payer perspective. A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [primary and recurrent ischaemic strokes, systemic embolism, transient ischaemic attack, haemorrhage (intracranial, extracranial, and minor), acute myocardial infarction and death] and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospective study, published literature, and national statistics. Clinical events, summarized as events per 100 patient-years, quality-adjusted life years (QALYs), total costs, and incremental cost effectiveness ratios (ICER) were calculated. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages (0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 “real-world” prescribing) and fewer ischaemic strokes (4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 “real-world” prescribing) per 100 patient-years. The ICER of dabigatran etexilate was $10,440/QALY versus warfarin and $3,962/QALY versus “real-world” prescribing. This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients.

 
  • References

  • 1 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-988.
  • 2 Diringer MN, Edwards DF, Mattson DT. et al. Predictors of acute hospital costs for treatment of ischemic stroke in an academic center. Stroke 1999; 30: 724-728.
  • 3 Dulli DA, Stanko H, Levine RL. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology 2003; 22: 118-123.
  • 4 Slot KB, Berge E, Dorman P. et al. Impact of functional status at six months on long term survival in patients with ischaemic stroke: prospective cohort studies. Br Med J 2008; 336: 376-379.
  • 5 Frost L, Engholm G, Johnsen S. et al. Incident thromboembolism in the aorta and the renal, mesenteric, pelvic, and extremity arteries after discharge from the hospital with a diagnosis of atrial fibrillation. Arch Intern Med 2001; 161: 272-276.
  • 6 Singer DE, Albers GW, Dalen JE. et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 546S-592S.
  • 7 Lip GY, Huber K, Andreotti F. et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting. Thromb Haemost 2010; 103: 13-28.
  • 8 Cairns JA, Connolly S, McMurtry S. et al. Canadian cardiovascular society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol 2011; 27: 74-90.
  • 9 Hylek EM, Skates SJ, Sheehan MA. et al. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996; 335: 540-546.
  • 10 Fang MC, Chang Y, Hylek EM. et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004; 141: 745-752.
  • 11 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: 857-867.
  • 12 van Walraven C, Jennings A, Oake N. et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006; 129: 1155-1166.
  • 13 Dolan G, Smith LA, Collins S. et al. Effect of setting, monitoring intensity and patient experience on anticoagulation control: a systematic review and meta-analysis of the literature. Curr Med Res Opin 2008; 24: 1459-1472.
  • 14 Rietbrock S, Plumb JM, Gallagher AM. et al. How effective are dose-adjusted warfarin and aspirin for the prevention of stroke in patients with chronic atrial fibrillation? An analysis of the UK General Practice Research Database. Thromb Haemost 2009; 101: 527-534.
  • 15 Parkash R, Wee V, Gardner MJ. et al. The impact of warfarin use on clinical outcomes in atrial fibrillation: a population-based study. Can J Cardiol 2007; 23: 457-461.
  • 16 Partington SL, Abid S, Teo K. et al. Pre-admission warfarin use in patients with acute ischemic stroke and atrial fibrillation: The appropriate use and barriers to oral anticoagulant therapy. Thromb Res 2007; 120: 663-669.
  • 17 Boehringer Ingelheim Canada Ltd.. Pradax™ Dabigatran Etexilate capsules product monograph. 2010 [cited 2011 March 11,]; Available at: http://www.boehringer-ingelheim.ca/en/Home/Human_Health/Our_Products/Product_Monographs/Pradax-pm.pdf
  • 18 Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb He-most 2009; 15 (Suppl. 01) 9S-16S.
  • 19 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
  • 20 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Newly identified events in the RE-LY Trial. N Engl J Med 2010; 363: 1875-1876.
  • 21 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.
  • 22 van Walraven C, Oake N, Wells PS. et al. Burden of potentially avoidable anticoagulant-associated hemorrhagic and thromboembolic events in the elderly. Chest 2007; 131: 1508-1515.
  • 23 Currie CJ, Jones M, Goodfellow J. et al. Evaluation of survival and ischaemic and thromboembolic event rates in patients with non-valvar atrial fibrillation in the general population when treated and untreated with warfarin. Heart 2006; 92: 196-200.
  • 24 Huybrechts KF, Caro JJ, Xenakis JJ. et al. The prognostic value of the modified Rankin Scale score for long-term survival after first-ever stroke. Results from the Athens Stroke Registry. Cerebrovasc Dis 2008; 26: 381-387.
  • 25 Lin HJ, Wolf PA, Kelly-Hayes M. et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27: 1760-1764.
  • 26 Ng YS, Stein J, Ning M. et al. Comparison of clinical characteristics and functional outcomes of ischemic stroke in different vascular territories. Stroke 2007; 38: 2309-2314.
  • 27 Hylek EM, Go AS, Chang Y. et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349: 1019-1026.
  • 28 Fang MC, Go AS, Hylek EM. et al. Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. J Am Geriatr Soc 2006; 54: 1231-1236.
  • 29 Hart RG, Benavente O, McBride R. et al. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999; 131: 492-501.
  • 30 Gage BF, Waterman AD, Shannon W. et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
  • 31 Roskell NS, Lip GY, Noack H. et al. Treatments for stroke prevention in atrial fibrillation: a network meta-analysis and indirect comparisons versus dabigatran etexilate. Thromb Haemost 2010; 104: 1106-1115.
  • 32 Statistics Canada.. Table 2a: Complete life table, Canada, 2000 to 2002: males. 2006 [cited 2010 May 19]; Available at: http://www.statcan.gc.ca/pub/84–537-x/t/pdf/4198612-eng.pdf
  • 33 Statistics Canada.. Table 2b: Complete life table, Canada, 2000 to 2002: females. 2006 [cited 2010 May 19]; Available at: http://www.statcan.gc.ca/pub/84–537-x/t/pdf/4198611-eng.pdf
  • 34 Office for National Statistics.. Interim Life Tables, United Kingdom 2005–2007. 2008 [cited November 2009]; Available at: http://www.statistics.gov.uk/downloads/theme_population/Interim_Life/ILTUK0608Reg.xls
  • 35 Walker AM, Bennett D. Epidemiology and outcomes in patients with atrial fibrillation in the United States. Heart Rhythm 2008; 5: 1365-1372.
  • 36 Rosand J, Eckman MH, Knudsen KA. et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004; 164: 880-884.
  • 37 Mant J, Hobbs FD, Fletcher K. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493-503.
  • 38 RateInflation.com.. Canada – Consumer Price Index (CPI) History. 2010 [cited 2010 May 24,]; Available at: http://www.rateinflation.com/consumer-price-index/canada-historical-cpi.php
  • 39 Total Pricing Systems Inc.. PPS Pharma Buyers Guide. Ontario Edition January 2011. Total Pricing Systems Inc, Moncton, NB, Canada; 2011.
  • 40 Schulman S, Anderson DR, Bungard TJ. et al. Direct and indirect costs of management of long-term warfarin therapy in Canada. J Thromb Haemost 2010; 8: 2192-2200.
  • 41 Mittmann N, Seung SJ, Sharma M. et al. Impact of disability status on ischaemic stroke costs (Poster P538). Poster presented at: 2010 International Stroke Congress, San Antonio, TX; Feb 25, 2010.
  • 42 Cadilhac DA, Carter R, Thrift AG. et al. Estimating the long-term costs of ischemic and hemorrhagic stroke for Australia: new evidence derived from the North East Melbourne Stroke Incidence Study (NEMESIS). Stroke 2009; 40: 915-921.
  • 43 Ghatnekar O, Persson U, Glader EL. et al. Cost of stroke in Sweden: an incidence estimate. Int J Technol Assess Health Care 2004; 20: 375-380.
  • 44 Mercaldi CJ, Ciarametaro M, Hahn B. et al. Cost efficiency of anticoagulation with warfarin to prevent stroke in medicare beneficiaries with nonvalvular atrial fibrillation. Stroke 2011; 42: 112-118.
  • 45 Goeree R, Blackhouse G, Petrovic R. et al. Cost of stroke in Canada: a 1-year prospective study. J Med Econ 2005; 8: 147-167.
  • 46 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.
  • 47 Tengs TO, Lin TH. A meta-analysis of quality-of-life estimates for stroke. Pharmacoeconomics 2003; 21: 191-200.
  • 48 Guidelines for the economic evaluation of health technologies: Canada. [3rd Edition]. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2006
  • 49 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.
  • 50 O’Brien CL, Gage BF. Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. J Am Med Assoc 2005; 293: 699-706.
  • 51 Ontario Drug Benefit Program.. Drugs Funded by Ontario Drug Benefit (ODB) Program: E-Formulary. 2011 [cited 2011 March 11]; Available at: http://www.health.gov.on.ca/english/providers/program/drugs/odbf_eformulary.html
  • 52 Canadian Institute for Health Information.. CIHI patient cost estimator. 2010 [cited 2010 October]; Available at: http://apps.cihi.ca/MicroStrategy/asp/Main.aspx?evt=2048001&src=Main.aspx.2048001&visualizationMode=0&server=torapprd30&project=Patient+Cost+Estimator+(PCE)&documentID= E9EE4A5211DED52F00100080562423A0&uid=pce_pub_en.
  • 53 Anis AH, Sun H, Singh S. et al. A cost-utility analysis of losartan versus atenolol in the treatment of hypertension with left ventricular hypertrophy. Pharmacoeconomics 2006; 24: 387-400.