Patient Care

Warfarin Initiation in Atrial Fibrillation Associated with Increased Short-Term Risk of Stroke


Clinical question: Is the initiation of warfarin associated with an increased risk of ischemic stroke in patients with atrial fibrillation (Afib)?

Background: Two Afib trials of oral factor Xa inhibitors showed an increased risk of stroke when patients were transitioned to open label warfarin at the end of the study. Warfarin can, theoretically, lead to a transient hypercoagulable state upon treatment initiation, so further study is indicated to determine if the initiation of warfarin is associated with increased stroke risk among Afib patients.

Study design: Population-based, nested case-control.

Setting: UK Clinical Practice Research Datalink.

Synopsis: A cohort of 70,766 patients with newly diagnosed Afib was identified from a large primary care database. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of stroke associated with warfarin monotherapy, classified according to time since initiation of treatment when compared to patients not on antithrombotic therapy.

Warfarin was associated with a 71% increased risk of stroke in the first 30 days of use (RR 1.71, 95% CI 1.39-2.12). Risk was highest in the first week of warfarin treatment, which is consistent with the known transient pro-coagulant effect of warfarin. Decreased risks were observed with warfarin initiation >30 days before the ischemic event (31-90 days: RR 0.50, 95% CI 0.34-0.75; >90 days: RR 0.55, 95% CI 0.50-0.61).

Limitations included the extraction of data from a database, which could lead to misclassification of diagnosis or therapy, and the observational nature of the study.

Bottom line: There may be an increased risk of ischemic stroke during the first 30 days of treatment with warfarin in patients with Afib.

Citation: Azoulay L, Dell-Aniello S, Simon T, Renoux C, Suissa S. Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes [published online ahead of print December 18, 2013]. Eur Heart J.

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