Non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants [NOACs] dabigatran, rivaroxaban, and apixaban) are safe and effective alternatives to warfarin for anticoagulant-naïve patients with atrial fibrillation, according to a study published in the BMJ.

No significant difference in ischemic stroke was observed between the NOACs and warfarin. Apixaban and dabigatran had significantly lower risks of death, any bleeding, and major bleeding compared with warfarin.

The study, led by Torben Bjerregaard Larsen, from Department of Cardiology at Aalborg University Hospital in Denmark, included 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 researchers confined their cohort to patients on warfarin (n=35,436; 57%), or those receiving standard dosages of NOACs: dabigatran 150 mg (n=12,701; 21%), rivaroxaban 20 mg (n=7,192; 12%), and apixaban 5 mg (n=6,349, 10%).

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Efficacy outcomes were defined as ischemic stroke; a composite of ischemic stroke or systemic embolism; death; and a composite of ischemic stroke, systemic embolism, or death. Safety outcomes included any bleeding, intracranial bleeding, and major bleeding.

The weighted rate for ischemic stroke or systemic embolism ranged from 2.9 to 3.9 per 100 person years for the NOACs and 3.3 for warfarin, representing no significant difference.

During 1 year of follow-up, rivaroxaban was associated with lower rates of ischemic stroke or systemic embolism compared with warfarin, with a hazard ratio of 0.83. Apixaban and dabigatran had significantly lower risks of death (5.3% and 2.7%, respectively) compared with warfarin (8.5%). The risk of death for rivaroxaban was 7.7%.

The annual rate of any bleeding was 3.3% for apixaban and 2.4% for dabigatran compared with 5.0% for warfarin and 5.3% for rivaroxaban.

“All NOACs are generally safe and effective alternatives to warfarin in a clinical care setting,” concluded the researchers.


  1. Larsen TB, Skjøth F, Nielsen PB, et al. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2016; 353:i3189.