Systemic Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Acute Middle Cerebral Artery Occlusion

Abstract

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 (Pϭ0.001). Only patients with recanalization improved neurologically (PϽ0.001). Because no symptomatic hemorrhage was observed, the power of our study to detect a symptomatic bleeding rate of Ն8% was at least 80%. Conclusions-Combined

Progressive Ischemic Stroke: Clinical Features and Evaluation of Short-and Long- Term Tirofiban Therapy

“…The progression occured on average 27.85 hours (6-72 hours) after the onset of stroke symptoms. The average NIHSS score at hour 1 of admission was 7.14 (2-6); the score at the time of progression occurence was 10.21 (5-21) with an average NIHSS increase of 3.07 (2-11); at 24 hours after administration of tirofiban, the score was 9.79 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and on discharge the score was 9.46 (1-18) (Figure 1). In the evaluation of the patient groups in terms of stroke subtypes, the NIHSS score was found to be highest in the cardioembolic stroke group and lowest in the small vessel disease group.…”

“…Thus, the target of gpIIb/IIIa antagonists is not thrombolysis and arterial recanalization, but the prevention of arterial reocclusion (14). As a consequence, thrombolytics have been combined with gpIIb/IIIa inhibitors in acute cerebral ischemia both in animal models and in human stroke (15,16).…”

“…The criteria for inclusion in the study were: presence of minor or medium-degree stroke on admission [with National Institute of Health Stroke Scale (NIHSS) score of [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18], final diagnosis of PIS, age range of 18-80, contraindication for thrombolytic therapy, tirofiban use for therapy, and reachable control data at the end of the 3. month. The criteria for exclusion from the study were history of cerebral or extracerebral hemorrhage, known intracranial disease (such as arteriovenous malformation, neoplasm, aneurysm), liver disease, thrombocytopenia (platelet number <100.000), platelet dysfunction, major trauma, major surgery in the last 3 months, and past stroke; coagulopathy [prothrombin time (PT) >1.3 times of the normal and international normalized ratio (INR) >1.3].…”

Improving reperfusion therapy for acute ischaemic stroke

“…Combined therapy resulted in a high rate (68%) of MCA recanalisation on MR angiography, greater salvage of perfusion MR defined tissue at risk, and better clinical outcome than standard IV tPA [66,67]. Low rates of symptomatic ICH were observed.…”

Reperfusión en el ictus isquémico agudo: estado actual y futuro

“…Se ha realizado algún estudio con inhibidores de la glicoproteína IIbIIIa, como el abciximab (estudio AbESTT II 39 ), con mayores tasas de recanalización arterial pero también de transformación hemorrá-gica, con un balance global riego/beneficio negativo. Otros estudios de series cortas de pacientes presentan prometedores resultados con el tirofiban 40 , que deberán ser contrastados en ensayos clínicos. Otros están ya en marcha con el eptifibatide, el CLEAR y el ROSIE-2.…”