Oral Anticoagulants vs. Warfarin for Atrial Fibrillation

Study Questions:

What is the comparative effectiveness and safety of the nonvitamin K oral anticoagulants (novel oral anticoagulants [NOACs] or dual oral anticoagulants [DOACs]) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulation-naïve patients with atrial fibrillation (AF)?


The authors conducted an observational nationwide cohort study using three Danish databases between August 2011 and October 2015. A total of 61,678 patients with nonvalvular AF without prior anticoagulation use for 1 year were included. The efficacy outcomes were ischemic stroke or systemic embolism, death, and the composite outcome of ischemic stroke, systemic embolism, or death. The safety outcomes were any bleeding, intracranial bleeding, and major bleeding. Inverse probability weighting for treatment selection was used in propensity adjustment to compare the different treatment groups. Event rates were calculated after 2.5 years of follow-up.


The study population included patients on warfarin (35,436, 57%), dabigatran 150 mg (12,701, 21%), rivaroxaban 20 mg (7,192, 12%), and apixaban 5 mg (6,349, 10%). After propensity adjustment, ischemic stroke or systemic embolism rates were 2.33, 2.32, 2.21, and 3.32 per 100 patient-years for warfarin, dabigatran, rivaroxaban, and apixaban, respectively. Only rivaroxaban had a lower risk of ischemic stroke or systemic embolism as compared to warfarin (adjusted hazard ratio [aHR], 0.83; 95% confidence interval [CI], 0.69-0.99). The composite efficacy endpoint (ischemic stroke, systemic embolism, or death) risk was lower for all three NOACs as compared to warfarin (aHR, 0.78 [0.64-0.94] for dabigatran, 0.87 [0.79-0.96] for rivaroxaban, and 0.79 [0.70-0.88] for apixaban). Adjusted major bleeding rates were 2.98, 2.02, 3.27, and 2.15 per 100 patient-years for warfarin, dabigatran, rivaroxaban, and apixaban, respectively. Dabigatran (aHR, 0.58 [0.47-0.72]) and apixaban (aHR, 0.61 [0.49-0.75]) both had lower risk of major bleeding as compared to warfarin.


The authors concluded that all NOACs appear to be safe and efficacious alternatives to warfarin for stroke prevention in nonvalvular AF.


Leveraging a large nationwide cohort of patients, the authors were able to demonstrate similar efficacy with improved safety for many of the NOAC/DOAC medications as compared to warfarin for stroke prevention in nonvalvular AF. Unlike meta-analyses of the randomized trials which demonstrated mortality benefit for the NOACs over warfarin in AF, this real-world unselected population only demonstrated similar risk of death, but lower risks of combined stroke and death. Along with lower risks of major bleeding, this should reassure clinicians about the efficacy and safety of these medications, even when a true ‘reversal’ agent is not available. It should be noted that this study limited the analysis to standard doses of NOAC medications and in a single Scandinavian country. Care should be taken when extrapolating these findings to patients using lower NOAC doses or to populations with broader ethnic diversity.

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