Systemic thrombolysis with recombinant tissue plasminogen activator and tirofiban in acute middle cerebral artery occlusion

Background and Purpose - 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 >= 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.