Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II).
OBJECTIVE
Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) improves the outcome for ischemic stroke patients who can be treated within 3 hours of symptom onset. The efficacy of thrombolysis has been demonstrated despite an increased risk of severe hemorrhagic transformation (HT) in patients treated with rtPA. We performed an analysis of risk factors for severe HT in the second European-Australasian Acute Stroke Study (ECASS II).


METHODS
HTs were classified by using clinical and radiological criteria as follows: hemorrhagic infarction (HI), parenchymal hemorrhage (PH), and symptomatic intracranial hemorrhage (SICH). Potential risk factors for HT were tested by stepwise logistic regression analysis, including rtPA-by-variable interactions. In addition, the distribution of bad outcome (modified Rankin score 5 to 6) at day 90 was stratified according to each category of HT.


RESULTS
PH and SICH but not HI were associated with rtPA. Also, PH and SICH but not HI were more severe in rtPA-treated patients than in those receiving placebo. Risk factors for PH were rtPA, extent of parenchymal hypoattenuation on baseline CT, congestive heart failure, increasing age, and baseline systolic blood pressure. The risk of PH on rtPA was increased in older patients and in those who were treated with aspirin before thrombolysis. Risk factors for SICH were rtPA, congestive heart failure, extent of parenchymal hypoattenuation, and increasing age. The risk of SICH on rtPA was increased in patients who were treated with aspirin before thrombolysis.


CONCLUSIONS
This secondary analysis of ECASS II has confirmed the importance of the extent of hypoattenuation as a risk factor for severe HT. The findings also suggest that older patients and those who have used aspirin before stroke are at higher risk of a severe HT on rtPA.
Larrue
V
V
Department of Neurology, University of Toulouse, Toulouse, France. larrue.v@chu-toulouse.fr
von Kummer R
R
R
Müller
A
A
Bluhmki
E
E
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects; D001794:Blood Pressure; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000209:etiology*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011859:Radiography; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment / Q000706:statistics & numerical data; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D001241:Aspirin