Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR

Introduction: Current guidelines allow the administration of intravenous recombinant tissue plasminogen activator (IV r-tPA) to warfarin-treated patients with acute ischemic stroke (AIS) who have an international normalized ratio (INR) of ≤1.7. However, concerns remain about the safety of using IV r-tPA in this situation due to a conceivable risk of symptomatic intracranial hemorrhage (sICH), lack of dedicated randomized controlled trials and the conflicts in the available data. We aimed to determine the risk of sICH in warfarin-treated patients with subtherapeutic INR who received IV r-tPA for AIS in our large volume comprehensive center.

Methods: Patients who had received IV r-tPA for AIS in a 9.6-year period were retrospectively investigated (n = 834). Patients taking warfarin prior to presentation were identified (n = 55). One patient was excluded due to elevated INR beyond the acceptable range for IV r-tPA treatment. Because of the significant difference in the sample size (54 vs 779), warfarin group was matched with 54 non-warfarin patients adjusted for independent risk factors for sICH (age, admission NIHSS, history of diabetes). Good outcome was defined as mRS of 0-2 on discharge and sICH was defined as an ICH causing increase in NIHSS ≥4 or death. Warfarin-treated group was further dichotomized based on INR (1-1.3 vs 1.3-1.7) and safety and outcome measures were compared between resultant groups.

Results: No significant difference was found between warfarin-treated and the non-warfarin groups in terms of chance of good outcome on discharge (27.8% in warfarin group vs 26.4% in non-warfarin group; p-value >0.05), or the rate of occurrence of sICH (3.7% in warfarin group vs 11.1% in non-warfarin group; p-value >0.05). Furthermore, rate of sICH (5.1% in patients with INR <1.3 versus 0.0% in patients with INR 1.3-1.7; p-value >0.05) or chance of good outcome on discharge (28.2% of patients with INR <1.3 versus 26.7% in patients with INR 1.3-1.7; p-value >0.05) were not found to be different after the warfarin-treated group was dichotomized.

Conclusion: Administration of IV r-tPA for AIS in warfarin-treated patients with subtherapeutic INR <1.7 does not increase the risk of sICH.