Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.
OBJECTIVE
To analyze the frequency, clinical characteristics, and predictors of symptomatic intracerebral hemorrhage (ICH) after intraarterial (IA) thrombolysis with recombinant pro-urokinase (r-proUK) in acute ischemic stroke.


METHODS
The authors conducted an exploratory analysis of symptomatic ICH from a randomized, controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset. Patients (n = 180) were randomized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone. As opposed to intention to treat, this analysis was based on "treatment received" and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent. The remaining six patients received out-of-protocol urokinase and were excluded from analysis. The authors analyzed centrally adjudicated ICH with associated neurologic deterioration (increase in NIH Stroke Scale [NIHSS] score of > or =4 points) within 36 hours of treatment initiation.


RESULTS
Symptomatic ICH occurred in 12 of 110 patients (10.9%) treated with r-proUK and in two of 64 (3.1%) receiving heparin alone. ICH symptoms in r-proUK-treated patients occurred at a mean of 10.2 +/- 7.4 hours after the start of treatment. Mortality after symptomatic ICH was 83% (10/12 patients). Only blood glucose was significantly associated with symptomatic ICH in r-proUK-treated patients based on univariate analyses of 24 variables: patients with baseline glucose >200 mg/dL experienced a 36% risk of symptomatic ICH compared with 9% for those with < or =200 mg/dL (p = 0.022; relative risk, 4.2; 95% CI, 1.04 to 11.7).


CONCLUSIONS
Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality. The risk of symptomatic ICH may be increased in patients with a blood glucose >200 mg/dL at stroke onset.
Kase
C S
CS
Department of Neurology, Boston University School of Medicine, MA 02118, USA. cskase@bu.edu
Furlan
A J
AJ
Wechsler
L R
LR
Higashida
R T
RT
Rowley
H A
HA
Hart
R G
RG
Molinari
G F
GF
Frederick
L S
LS
Roberts
H C
HC
Gebel
J M
JM
Sila
C A
CA
Schulz
G A
GA
Roberts
R S
RS
Gent
M
M
D000208:Acute Disease; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011994:Recombinant Proteins / Q000009:adverse effects*; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects* / Q000706:statistics & numerical data; D014568:Urokinase-Type Plasminogen Activator / Q000009:adverse effects*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase