title: Systemic thrombolysis with recombinant tissue plasminogen activator and tirofiban in acute middle cerebral artery occlusion.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Straub
authors.forename: Ulrich
authors.initials: U
authors.lastname: Junghans
authors.forename: Verica
authors.initials: V
authors.lastname: Jovanovic
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Wittsack
authors.forename: Rüdiger J
authors.initials: RJ
authors.lastname: Seitz
authors.forename: Mario
authors.initials: M
authors.lastname: Siebler
mesh_terms: 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*
chemical_list: D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D014443:Tyrosine; D010959:Tissue Plasminogen Activator; D000077466:Tirofiban