Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke: pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II Trials.
OBJECTIVE
A number of factors have been associated with postthrombolysis intracerebral hemorrhage, but these have varied across studies.


METHODS
We examined patients with acute ischemic stroke treated with intravenous tissue plasminogen activator within 3 hours of symptom onset who were enrolled in the placebo arms of 2 trials (Stroke-Acute Ischemic NXY Treatment [SAINT] I and II Trials) of a putative neuroprotectant. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). Post-tissue plasminogen activator symptomatic intracerebral hemorrhage was defined as a worsening in National Institutes of Health Stroke Scale of > or =4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days.


RESULTS
Symptomatic intracerebral hemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator. In multivariable analysis, symptomatic intracerebral hemorrhage was increased with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 3.28 to 26.32, P<0.001), higher National Institutes of Health Stroke Scale score (OR, 1.09 per point, 1.03 to 1.15, P=0.002), and CT changes defined by ASPECTS (ASPECTS 8 to 9: OR, 2.26, 0.63 to 8.10, P=0.21; ASPECTS < or =7: OR, 5.63, 1.66 to 19.10, P=0.006). Higher National Institutes of Health Stroke Scale was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 0.79 to 0.85, P<0.001). There was no relationship between baseline antiplatelet use or CT changes and clinical outcome.


CONCLUSIONS
Along with higher National Institutes of Health Stroke Scale and extensive early CT changes, baseline antiplatelet use (particularly double antiplatelet therapy) was associated with an increased risk of post-tissue plasminogen activator symptomatic intracerebral hemorrhage. Of these factors, only National Institutes of Health Stroke Scale was associated with clinical outcome.
Cucchiara
Brett
B
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA. cucchiar@mail.med.upenn.edu
Kasner
Scott E
SE
Tanne
David
D
Levine
Steven R
SR
Demchuk
Andrew
A
Messe
Steven R
SR
Sansing
Lauren
L
Lees
Kennedy R
KR
Lyden
Patrick
P
D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000175:diagnosis; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator