Stroke Risk During Warfarin Initiation for Atrial Fibrillation

Study Questions:

What are the risks of ischemic stroke during initiation of warfarin therapy for patients with atrial fibrillation (AF) as compared to AF patients not treated with anticoagulation?


Using a large insurance database, the authors identified AF patients in 2009 and 2010 and then created two propensity-matched cohorts: The treatment group included patients treated with warfarin and the control group consisted of patients not treated with anticoagulants. Patients were followed for a median of 415 days and ischemic stroke events were identified and analyzed using Cox regression. Ischemic stroke rates were calculated on a yearly basis for comparison.


AF patients initiating on warfarin experienced a nonsignificantly higher rate of ischemic stroke than control patients in the first 30 days (1.47%/year vs. 0.98%/year; adjusted hazard ratio [aHR], 1.46 [0.80-2.65]). However, after the first 30 days, warfarin-treated patients experienced a lower rate of ischemic stroke than controls (0.81%/year vs. 1.09%/year; aHR, 0.70 [0.57-0.85]). Warfarin-treated patients experienced a higher rate of major bleeding than controls in both the first 30 days (4.91%/year vs. 3.20%/year; aHR, 1.42 [1.02-1.97]) and beyond 30 days (4.64%/year vs. 4.10%/year; aHR, 1.13 [1.03-1.23]).


The authors concluded that warfarin’s effect was qualitatively different and consistent with a modest increase in stroke risk during the first 30 days after initiation than in the subsequent period.


Recent studies have focused on reducing the overall number of antithrombotic agents given to AF patients. In line with that thinking, most AF patients initiating on warfarin are not given any form of heparin bridging. However, this study suggests that patients might have a slightly higher ischemic stroke risk during warfarin initiation as compared to a maintenance period. Experts have described a hypothetical prothrombotic state during warfarin initiation related to the variable half-lives of the inhibited clotting factors (II, VII, IX, and X) and proteins (C and S). However, the results of this study are not conclusive and are of small enough magnitude that standard of care should not be changed yet for AF patients initiating on warfarin. Similar analyses among patients initiating on direct oral anticoagulants (DOACs; apixaban, dabigatran, edoxaban, and rivaroxaban) remain to be tested. Nonetheless, the rapid onset and single thrombotic targets of DOACs may theoretically mitigate this hypothetical prothrombotic risk in the first 30 days of therapy.

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

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Blood Coagulation Factors, Fibrinolytic Agents, Heparin, Ischemia, Risk Factors, Standard of Care, Stroke, Vascular Diseases, Warfarin

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