Glycoprotein IIb/IIIa antagonists in acute ischaemic stroke: current status and future directions.
Glycoprotein (GP) IIb/IIIa receptors on the surface of platelets play a critical role in thrombosis. Intravenous GP IIb/IIIa antagonists abciximab, tirofiban and eptifibatide have demonstrated efficacy in acute coronary syndromes when combined with heparin, aspirin, clopidogrel and percutanous coronary interventions. Results have been less consistent in acute ischaemic stroke. Preclinical data support the potential benefit of these agents both in the microcirculation and in aiding clot lysis. While phase I and II trials of abciximab as the sole agent employing dosages comparable with those used in coronary syndromes were promising, the pivotal phase III trial was abandoned because of an unfavourable benefit-to-risk ratio. New preliminary platelet inhibition measurements from our group suggest that cardiac dosages were likely to be too high for stroke patients. Exploration of lower dosages of abciximab and potentiation with time-limited weight-based heparin along with platelet aggregation inhibition measurement is continuing on a smaller scale. At present, the most common usage of GP IIb/IIIa antagonists in stroke are as adjunctive agents to thrombolysis by intravenous and intra-arterial routes. Substantial progress is likely to require a better understanding of the mechanism of actions and unique pharmacology of GP IIb/IIIa antagonists in ischaemic stroke.
Mandava
Pitchaiah
P
Michael E. DeBakey VA Medical Center and Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA. pmandava@bcm.tmc.edu
Thiagarajan
Perumal
P
Kent
Thomas A
TA
D000077284:Abciximab; D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D000077542:Eptifibatide; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000188:drug therapy*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab