DOACs vs. warfarin for afib

Short Attention Span Summary

What they found
Direct oral anticoagulants are increasingly used over warfarin. Many are still difficult to reverse or have no reversal agent.  Despite this, some studies suggest they may still be safer than warfarin and more effective.  This was a national observational cohort study from Denmark comparing warfarin and either rivaroxaban, apixaban, or dabigatran in patients with atrial fibrillation.  Risk of ischemic stroke or systemic embolism was less with rivaroxaban compared with warfarin.  Risk of death was less with apixaban and dabigatran compared to warfarin but not rivaroxaban.  Risk of any bleeding was lower with apixaban and dabigatran compared with warfarin but the same with rivaroxaban.

Take Home
It's hard to pick a clear winner among the four agents as far as effectiveness.  All the direct agents have the advantage of no routine INR monitoring and fewer drug interactions compared with warfarin.  Rivaroxaban appears to be as safe as warfarin; apixaban and dabigatran appear to be safer than warfarin.  Journal Watch has a nice summary as well.  Evidence Care has a helpful table comparing the DOACs in the PE trials.


Abstract

BMJ. 2016 Jun 16;353:i3189. doi: 10.1136/bmj.i3189.

Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.

Larsen TB1, Skjøth F2, Nielsen PB3, Kjældgaard JN3, Lip GY4.

Author information:

1Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark tobl@rn.dk.

2Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark Unit for Clinical Biostatistics and Bioinformatics, Aalborg University Hospital, Aalborg, Denmark.

3Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.

4Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK.

Abstract

OBJECTIVE:

 To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation.

DESIGN:

 Observational nationwide cohort study.

SETTING:

 Three Danish nationwide databases, August 2011 to October 2015.

PARTICIPANTS:

 61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%).

MAIN OUTCOME MEASURES:

 Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding.

RESULTS:

 When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5.3%).

CONCLUSION:

All NOACs seem to be safe and effective alternatives to warfarin in a routine care setting. No significant difference was found between NOACs and warfarin for ischaemic stroke. The risks of death, any bleeding, or major bleeding were significantly lower for apixaban and dabigatran compared with warfarin.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PMCID: PMC4910696 Free PMC Article

PMID: 27312796 [PubMed - in process]