Tools for Practice Outils pour la pratique


#39 Dabigatran versus Warfarin in Atrial Fibrillation


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


BOTTOM LINE
RÉSULTAT FINAL
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.



CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session



EVIDENCE
DONNÉES PROBANTES
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


Latest Tools for Practice
Derniers outils pour la pratique

#359 Topical corticosteroids for atopic dermatitis - More than skin deep

What are the benefits/harms of topical corticosteroids for atopic dermatitis in adults/children?
Read Lire 0.25 credits available Crédits disponibles

#358: Any berry good solutions to preventing UTIs: Cranberries?

Do cranberry products prevent recurrent urinary tract infections (UTIs)?
Read Lire 0.25 credits available Crédits disponibles

#357: Overcoming Resistance: Antipsychotics for difficult to treat depression

In patients with treatment-resistant depression, is adding an atypical antipsychotic to current therapy safe and effective?
Read Lire 0.25 credits available Crédits disponibles

This content is certified for MainPro+ Credits, log in to access

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session


Author(s)
Auteur(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.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.