Tools for Practice


#39 Dabigatran versus Warfarin in Atrial Fibrillation


CLINICAL QUESTION
What are the benefits and risks of dabigatran (Pradaxa®) compared to warfarin, in patients with atrial fibrillation?

BOTTOM LINE
Dabigatran offers some advantages over warfarin (example ~0.6%/year fewer strokes), but benefits decline as warfarin time in INR range improves. If using Dabigatran 150mg bid is generally recommended.


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EVIDENCE
Randomized Controlled Trial (RCT)1,2 of 18,113 patients given dabigatran 110 mg BID or 150 mg BID, or warfarin. Primary outcome: Stroke or systemic embolism.  Net benefit outcome: Stroke, systemic or pulmonary embolism, MI, death, or major hemorrhage.
  • 63% male, mean age 71 years, mean CHADS2 2.1. INR in range 64% of time for warfarin patients.
  • Dabigatran 150mg BID versus warfarin (events per year):
    • Dabigatran improved primary outcome (1.1% vs. 1.7%), Number Needed to Treat (NNT)=167.
    • Dabigatran improved net benefit (6.9% vs. 7.6%), NNT=137.
    • No difference in death or major bleed, but trend favoured dabigatran.
    • Dabigatran had non-statistically significant increase in myocardial infarctions (0.8% vs. 0.6%).
  • Dabigatran 110 mg BID vs. warfarin (events per year):
    • No difference in primary outcome, death, myocardial infarction, or net benefit.
    • Dabigatran had fewer major bleeds (2.9% vs 3.6%) NNT=143.
  • More patients stopped dabigatran (21%) than warfarin (17%) at two years.
  • Early RCT of dabigatran versus warfarin was too short (12 weeks) with too few patients (502) to assess meaningful clinical outcomes.3
Context: 
  • Potential risk of myocardial infarction: Number Needed to Harm ~400-500/year.4,5
  • Dabigatran increases the risk of bleeding and thromboembolism in mechanical heart valves.6
  • Benefits of dabigatran over warfarin declined (or disappeared) the more INR was in range (in the warfarin group).7
  • Prescribing considerations:8,9
    • Dabigatran contraindicated: Creatinine clearance (CrCl) <30 ml/minute, patients on ketoconazole.
    • Drug interactions can occur with P-glycoprotein inhibitors (including verapamil, amiodarone, and quinidine).
    • Dabigatran 150 mg BID recommended but consider 110 mg bid for patients >80 years, or patients >75 years old with risk factors for bleeding, diminished renal function (CrCl 30-50 ml/ minute).
    • If switching from warfarin to dabigatran, do when INR <2.0.
  • Cost effectiveness analysis suggest dabigatran 150 mg is cost effective.10,11
January 4, 2011

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Author(s):

  • Christina Korownyk MD CCFP
  • G. Michael Allan MD CCFP
  • Michael R Kolber MD CCFP MSc
  • Tammy Bungard BSP PharmD

1. Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med. 2009; 361:1139-51.

2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med. 2010; 363(19):1875-6.

3. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Am J Cardiol. 2007; 100:1419-26.

4. Artang R, Rome E, Neilsen JD, et al. Am J Cardiol. 2013; 112(12):1973-9.

5. Kolber MR, Bungard T. Tools for Practice #73. 2012. Available at: https://www.acfp.ca/wp-content/uploads/tools-for-practice/1397838716_20120926_110119.pdf. Accessed February 10, 2015.

6. Eikelboom JW, Connolly SJ, Brueckmann M, et al. N Engl J Med. 2013; 369:1206-14.

7. Wallentin L, Yusuf S, Ezekowitz MD, et al. Lancet. 2010; 376:975-83.

8. Gage BF. N Engl J Med. 2009; 361(12):1200-2.

9. Pradaxa® (Product Monograph on the Internet). Burlington, ON; Boehringer Ingelheim, 2015. Available from: http://www.boehringer-ingelheim.ca/content/dam/internet/opu/ca_EN/documents/humanhealth/product_monograph/PradaxaPMEN.pdf. Accessed February 10, 2015.

10. Limone BL, Baker WL, Kluger J, et al. PLoS ONE. 2013; 8(4):e62183.

11. Coyle D, Coyle K, Cameron C, et al. Value Health. 2013; 16(4):498-506.

Authors do not have any conflicts of interest to declare.