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


OBJECTIVE
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Duke Clinical Research Institute, Durham, NC 27715, USA.
Ying
Y
Xian
Li
L
Liang
Eric E
EE
Smith
Lee H
LH
Schwamm
Mathew J
MJ
Reeves
DaiWai M
DM
Olson
Adrian F
AF
Hernandez
Gregg C
GC
Fonarow
Eric D
ED
Peterson
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D002545:Brain Ischemia / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages; D008297:Male; D012042:Registries / Q000706:statistics & numerical data; D012306:Risk; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014859:Warfarin / Q000009:adverse effects*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D014859:Warfarin; D010959:Tissue Plasminogen Activator