Systemic thrombolysis with recombinant tissue plasminogen activator and tirofiban in acute middle cerebral artery occlusion.
OBJECTIVE
In acute ischemic stroke, thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) is limited by a concomitant activation of the coagulatory system, leading to incomplete or delayed reperfusion, microcirculatory disturbances, or even repeated vessel occlusions. Our pilot study sought to assess the therapeutic potential of a new treatment strategy combining rtPA at reduced dosages with a platelet glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitory agent in acute middle cerebral artery occlusion.


METHODS
Nineteen patients suffering from acute middle cerebral artery occlusion (Thrombolysis in Myocardial Infarction [TIMI] flow grade 0 to 1) underwent combined intravenous thrombolytic treatment using rtPA at reduced dosages and the GPIIb/IIIa antagonist tirofiban. Stroke MRI (diffusion- and perfusion-weighted imaging) and MR angiography were performed at baseline and between days 1 and 2 after treatment. Clinical scores (National Institutes of Health Stroke Scale and modified Rankin Scale) were assessed at baseline and after 1 week.


RESULTS
Middle cerebral artery recanalization (TIMI flow grade 2 and 3) occurred in 13 of 19 patients (68%). The ischemic lesion on follow-up MRI was significantly smaller in patients with recanalization compared with those without recanalization (P=0.001). Only patients with recanalization improved neurologically (P<0.001). Because no symptomatic hemorrhage was observed, the power of our study to detect a symptomatic bleeding rate of > or =8% was at least 80%.


CONCLUSIONS
Combined thrombolysis with a GPIIb/IIIa antagonist and rtPA at reduced dosages is promising but cannot be recommended for general use before prospective randomized clinical trials are completed.
Straub
Stefan
S
Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany.
Junghans
Ulrich
U
Jovanovic
Verica
V
Wittsack
Hans J
HJ
Seitz
Rüdiger J
RJ
Siebler
Mario
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D038524:Diffusion Magnetic Resonance Imaging; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000175:diagnosis / Q000188:drug therapy*; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D000077466:Tirofiban; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D014443:Tyrosine; D010959:Tissue Plasminogen Activator; D000077466:Tirofiban