Risks of Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Receiving Warfarin and Treated With Intravenous Tissue Plasminogen Activator

Study Questions:

What is the risk of symptomatic intracranial hemorrhage (sICH) among patients with ischemic stroke treated with intravenous tissue plasminogen activator (tPA) who were receiving warfarin versus those who were not, and degree of this risk as a function of international normalized ratio (INR)?


This was an observational study, using data from the American Heart Association Get With The Guidelines–Stroke Registry, of 23,437 patients with ischemic stroke and with INR of 1.7 or lower, treated with intravenous tPA in 1,203 registry hospitals from April 2009 through June 2011. The main outcome measure was sICH. Secondary endpoints include life-threatening/serious systemic hemorrhage, any tPA complications, and in-hospital mortality.


Overall, 1,802 (7.7%) patients with stroke treated with tPA were receiving warfarin (median INR, 1.20; interquartile range [IQR], 1.07-1.40). Warfarin-treated patients were older, had more comorbid conditions, and had more severe strokes. The unadjusted sICH rate in warfarin-treated patients was higher than in non–warfarin-treated patients (5.7% vs. 4.6%, p < 0.001), but these differences were not significantly different after adjustment for baseline clinical factors (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.82-1.25). Similarly, there were no significant differences between warfarin-treated and non–warfarin-treated patients for serious systemic hemorrhage (0.9% vs. 0.9%; adjusted OR, 0.78; 95% CI, 0.49-1.24), any tPA complications (10.6% vs. 8.4%; adjusted OR, 1.09; 95% CI, 0.93-1.29), or in-hospital mortality (11.4% vs. 7.9%; adjusted OR, 0.94; 95% CI, 0.79-1.13). Among warfarin-treated patients with INRs of 1.7 or lower, the degree of anticoagulation was not statistically significantly associated with sICH risk (adjusted OR, 1.10 per 0.1-unit increase in INR; 95% CI, 1.00-1.20; p = 0.06).


The authors concluded that among patients with ischemic stroke, the use of intravenous tPA among warfarin-treated patients (INR ≤1.7) was not associated with increased sICH risk compared with non–warfarin-treated patients.


The study reports that the use of intravenous tPA among warfarin-treated patients with a baseline INR of 1.7 or lower was not associated with increased risk of sICH. These findings were robust across several subgroup analyses and risk-adjustment methods. Warfarin use was also not associated with life-threatening or serious systemic hemorrhage, any tPA complication, or in-hospital mortality. Overall, these data support current American Heart Association/American Stroke Association guideline recommendations and confirm the safety profile of intravenous tPA in warfarin-treated patients with INRs of 1.7 or lower in routine clinical practice. The real risk is in not treating otherwise eligible patients, who may then have prolonged morbidity from their stroke.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism

Keywords: International Normalized Ratio, Stroke, Intracranial Hemorrhages, Warfarin, Tissue Plasminogen Activator

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