Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator

JAMA. 2012 Jun 27;307(24):2600-8. doi: 10.1001/jama.2012.6756.


Context: Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, patients receiving long-term chronic warfarin therapy may face an increased risk for intracranial hemorrhage when treated with tPA. Although current guidelines endorse administering intravenous tPA to warfarin-treated patients if their international normalized ratio (INR) is 1.7 or lower, there are few data on safety of intravenous tPA in warfarin-treated patients in clinical practice.

Objectives: To determine the risk of symptomatic intracranial hemorrhage (sICH) among patients with ischemic stroke treated with intravenous tPA who were receiving warfarin vs those who were not and to determine this risk as a function of INR.

Design, setting, and patients: 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 1203 registry hospitals from April 2009 through June 2011.

Main outcome measure: Symptomatic intracranial hemorrhage. Secondary end points include life-threatening/serious systemic hemorrhage, any tPA complications, and in-hospital mortality.

Results: Overall, 1802 (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 < .001), but these differences were not significantly different after adjustment for baseline clinical factors (adjusted odds ratio [OR], 1.01 [95% 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 = .06).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Brain Ischemia / epidemiology*
  • Case-Control Studies
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Hospital Mortality
  • Humans
  • Infusions, Intravenous
  • International Normalized Ratio
  • Intracranial Hemorrhages
  • Male
  • Registries / statistics & numerical data
  • Risk
  • Stroke / drug therapy*
  • Tissue Plasminogen Activator / administration & dosage*
  • Warfarin / adverse effects*


  • Anticoagulants
  • Fibrinolytic Agents
  • Warfarin
  • Tissue Plasminogen Activator