Abstract 10: Intracranial Hemorrhage Risks among Warfarin Treated Acute Ischemic Stroke Patients Receiving Thrombolytic Therapy

Abstract

Background While intravenous thrombolytic therapy (tPA) improves the outcomes of ischemic stroke, treatment of those receiving warfarin raises concerns regarding symptomatic intracranial hemorrhage (ICH). While guidelines suggest excluding patients with an international normalized ratio (INR) >1.7, little is known about the use and safety of tPA in warfarin-treated patients in clinical practice. Methods Data from 23,437 ischemic stroke patients treated with tPA with an INR ≤1.7 in 1,203 Get With The Guidelines-Stroke hospitals between April 2009 and June 2011. Multivariable logistic regression analysis was performed to evaluate the association of preadmission warfarin use on ICH risk while adjusting for potential confounders. Results Overall 1,802 (7.7%) were taking warfarin prior to admission. Warfarin treated patients were older (median 77 vs. 71 years, p<0.001) and had more comorbid illness and greater stroke severity (median National Institutes of Health Stroke Scale 14 vs. 11, p<0.001). Crude rates of ICH were higher in those taking warfarin 5.7% vs. 4.7% (unadjusted OR 1.22, 95% CI 0.99-1.51). However, after risk adjustment, ICH risks were similar (adjusted OR 1.01, 95% CI 0.82-1.25). These findings were consistent across several sensitivity analyses (Table). There were no significant differences between warfarin and non-warfarin users for serious systemic hemorrhage (0.9% vs. 0.9%; adjusted OR 0.78; 95% CI 0.48-1.24), any tPA complications (10.6% vs. 8.4%; adjusted OR 1.09; 95% CI 0.93-1.29), and in-hospital mortality (11.4% vs. 7.9%; adjusted OR 0.94; 95% CI 0.79-1.13). Among those receiving warfarin, a trend toward higher crude ICH rates was observed among those with higher baseline INR levels (Cochran-Mantel-Haenszel trend test, p=0.03). After adjustment for risk factors, higher INR levels had a marginally significant association with ICH risk (adjusted OR 1.10, 95% CI 1.00-1.20, p=0.06 for each 0.1 units increase in INR). Conclusion This represents the largest clinical experience of the safety of thrombolysis in warfarin treated patients who meets clinical guideline eligibility criteria. Use of intravenous tPA among warfarin-treated stroke patients (INR ≤1.7) was not associated with increased ICH risk compared to non-warfarin treated patients in routine clinical practice. These data provide empirical support of current AHA/ASA guideline recommendations.