Short-Term Risk of Bleeding and Stroke Events in Atrial Fibrillation Patients

Study Questions:

What are the safety and effectiveness data for direct oral anticoagulants (DOACs), dabigatran and rivaroxaban, as compared to vitamin K antagonists (VKAs) in anticoagulant-naïve nonvalvular atrial fibrillation (AF) patients during the early phase of anticoagulant therapy?


Using the nationwide French cohort, all nonvalvular AF patients who initiated on dabigatran or rivaroxaban between July and November 2012 were compared to propensity-matched patients initiating on a VKA between July and November 2011. Patients were followed up for 90 days until an outcome, death, or loss of follow-up through December 31 of the inclusion year. Hazard ratios for bleeding or arterial thromboembolic hospitalization were assessed using a Cox regression model in an intention-to-treat analysis.


Among 19,713 VKA, 8,443 dabigatran, and 4,651 rivaroxaban new users, patients were matched 2:1 between VKA and DOAC groups. Bleeding event rates were 3.3 and 3.7/100 person-years (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.64-1.21) for dabigatran- and VKA matched-treated patients, respectively, while stroke or systemic embolism event rates were 2.0 and 1.8/100 person-years (HR,1.10; 95% CI, 0.72-1.69), respectively. Bleeding events rates were 3.7 and 3.6/100 person-years (HR, 0.98; 95% CI, 0.64-1.51) for rivaroxaban- and VKA matched-treated patients, respectively, while stroke or systemic embolism event rates were 1.4 and 1.5/100 person-years (HR, 0.93; 95% CI, 0.47-1.85), respectively.


The authors concluded that there was no statistically significant difference in early bleeding or stroke rates between DOAC and VKA users. However, the authors also concluded that physicians should exercise caution when initiating either a DOAC or VKA in nonvalvular AF patients given the higher rates of bleeding as compared to thromboembolic events.


This study sheds light into the practice patterns of DOAC use in a French nationwide cohort, where younger and healthier patients were preferentially selected for DOAC therapy. However, after propensity matching, there did not appear to be a stroke or bleeding risk differential between VKA and DOAC medications. Care should be taken when interpreting these data, as they rely on billing diagnoses. Therefore, the severity of bleeding or thromboembolic events could not be assessed. Nevertheless, the rates of bleeding during the first 90 days of therapy were markedly higher than the rates of thromboembolic events in this inception cohort. Physicians should be aware of this risk differential when initiating AF patients on anticoagulant therapy, and should make attempts to mitigate bleeding risk wherever possible.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Embolism, Intention to Treat Analysis, Primary Prevention, Risk, Stroke, Thromboembolism, Vitamin K

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