Abstract 11085: Early Effects on Ischemic Strokes After Initiation of Warfarin in Patients With Atrial Fibrillation

Abstract

Introduction: A recent atrial fibrillation (AF) randomized controlled trial has reported an increased risk of stroke in the first 30 days after patients were transitioned from an oral factor Xa agent to warfarin. To date, little is known about the effect of warfarin initiation on subsequent stroke risk in patients with AF.

Hypothesis: Patients initiating warfarin may be at an increased risk of stroke in the first 30 days of use.

Methods: A population-based cohort of patients with chronic AF from the UK General Practice Research Database between 1993 and 2008 was formed. Using a nested case-control analysis, all cases of stroke occurring during cohort follow-up were matched with up to 10 controls based on age, sex, date of AF diagnosis, and time since AF diagnosis. Current warfarin use was classified according to time since initiation of treatment (within 30 days, between 31 to 90 days, and >90 days) and therapeutic range. The reference category consisted of non-users of any antithrombotic therapy for at least 1 year. Conditional logistic regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs), and all RRs were adjusted for CHADS₂ along with 14 other potential confounders.

Results: The cohort included 70,766 patients with chronic AF, of whom 5519 had a stroke during a mean follow-up of 3.7 years (overall rate: 2.0%/year). Warfarin was associated with a 72% increased risk of stroke in the first 30 days of use (RR: 1.72, 95% CI: 1.39-2.12). This increased risk of stroke was observed at all therapeutic ranges, and particularly among those within range (INR 2-3) (RR: 3.12, 95% CI: 1.69-5.77). A decreased risk was observed between 31 to 90 days and >90 days after warfarin initiation (RR: 0.50, 95% CI: 0.34-0.75, and RR: 0.55, 95% CI: 0.50-0.61, respectively). Such decreased risks were only observed among patients within therapeutic range.

Conclusions: These results are consistent with those of a recent trial, and indicate that patients initiating warfarin may be at an increased risk of stroke in the first 30 days of treatment. While residual confounding needs to be considered in this observational study, it is biologically plausible that warfarin induces a transient hypercoagulable state at the start of the treatment.