Therapeutic Potential of Platelet Glycoprotein IIb/IIIa Receptor Antagonists in Acute Ischaemic Stroke

Acute ischaemic stroke is the result of an abrupt interruption of focal cerebral blood flow. In the majority of cases, this interruption is caused by an acute thromboembolism. Based on clinical experience in the treatment of acute coronary syndromes, platelet glycoprotein (GP) IIb/IIIa receptor antagonists alone, in combination with reduced doses of thrombolytic agents, or as complementary therapy for short-term mechanical interventions merit consideration as a class of agents with potential use in ischaemic stroke. Research to date and extrapolation from the cardiac literature suggest significant, but as yet unproven, potential for the use of GP IIb/IIIa receptor antagonists in the treatment of acute ischaemic stroke. This potential exists both at the site of the thromboembolic occlusion and at the distal microvascular level. This article reviews the scientific rationale and available evidence for the potential use of platelet GP IIb/IIIa receptor antagonists in acute ischaemic stroke.

[1]  G. Lenzi,et al.  Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours , 1989, Journal of the Neurological Sciences.

[2]  H. Gold,et al.  A canine model of coronary artery thrombosis with superimposed high grade stenosis for the investigation of rethrombosis after thrombolysis. , 1989, Journal of the American College of Cardiology.

[3]  H. Gold,et al.  Lysis of plasminogen activator-resistant platelet-rich coronary artery thrombus with combined bolus injection of recombinant tissue-type plasminogen activator and antiplatelet GPIIb/IIIa antibody. , 1990, Journal of the American College of Cardiology.

[4]  S L Bacharach,et al.  Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Comparison of thallium scintigraphy with reinjection and PET imaging with 18F-fluorodeoxyglucose. , 1991, Circulation.

[5]  H. Gold,et al.  Animal models for arterial thrombolysis and prevention of reocclusion. Erythrocyte-rich versus platelet-rich thrombus. , 1991, Circulation.

[6]  M. Pessin,et al.  Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rt-PA Acute Stroke Study Group. , 1993, AJNR. American journal of neuroradiology.

[7]  R. Califf,et al.  Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study. , 1993, Journal of the American College of Cardiology.

[8]  J. Koziol,et al.  Fibrin Contributes to Microvascular Obstructions and Parenchymal Changes During Early Focal Cerebral Ischemia and Reperfusion , 1994, Stroke.

[9]  G. D. del Zoppo,et al.  P‐Selectin and Intercellular Adhesion Molecule‐1 Expression After Focal Brain Ischemia and Reperfusion , 1994, Stroke.

[10]  J. Garcìa,et al.  Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). , 1994, The American journal of pathology.

[11]  F. Neumann,et al.  Platelet activation and coronary stent implantation. Effect of antithrombotic therapy. , 1996, Circulation.

[12]  F. Neumann,et al.  Changes in membrane glycoproteins of circulating platelets after coronary stent implantation. , 1996, Heart.

[13]  F. Verheugt,et al.  Reocclusion: the flip side of coronary thrombolysis. , 1996, Journal of the American College of Cardiology.

[14]  G. Roubin,et al.  Angioplasty and stenting for restenosis after carotid endarterectomy. Initial experience. , 1996, Stroke.

[15]  R. Califf,et al.  Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators. , 1997, Circulation.

[16]  D. Phillips,et al.  Clinical pharmacology of eptifibatide. , 1997, The American journal of cardiology.

[17]  T. Investigators.  Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. , 1998, Lancet.

[18]  David P Miller,et al.  Abciximab therapy and unplanned coronary stent deployment: favorable effects on stent use, clinical outcomes, and bleeding complications. EPILOG Trial Investigators. , 1998, Circulation.

[19]  R. Higashida,et al.  PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism. , 1998, Stroke.

[20]  J. Zivin.  Factors determining the therapeutic window for stroke , 1998, Neurology.

[21]  E. Connolly,et al.  Reduced microvascular thrombosis and improved outcome in acute murine stroke by inhibiting GP IIb/IIIa receptor-mediated platelet aggregation. , 1998, The Journal of clinical investigation.

[22]  M Henry,et al.  Current global status of carotid artery stent placement. , 1998, Catheterization and cardiovascular diagnosis.

[23]  E. Topol.  Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade , 1998, The Lancet.

[24]  F. Neumann,et al.  Effect of Glycoprotein IIb-IIIa Receptor Antagonism on Platelet Membrane Glycoproteins after Coronary Stent Placement , 1998, Thrombosis and Haemostasis.

[25]  W D Heiss,et al.  Which targets are relevant for therapy of acute ischemic stroke? , 1999, Stroke.

[26]  R. Higashida,et al.  Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial , 1999 .

[27]  E. Antman,et al.  Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators. , 1999, Circulation.

[28]  F. Cecena,et al.  The Platelet IIb/IIIa Inhibitor Abciximab as Adjunctive Therapy in Carotid Stenting of Potential Thrombotic Lesions , 1999 .

[29]  J. Koziol,et al.  Integrin αIIbβ3 Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia , 2000 .

[30]  Abciximab in Ischemic Stroke Investigators.  Abciximab in acute ischemic stroke. A randomized, double-blind, placebo-controlled, dose-escalation study. , 2000, Stroke.

[31]  P. Akins,et al.  Intra-arterial prourokinase for acute ischemic stroke. , 2000, JAMA.

[32]  U Kaul,et al.  Elective stenting of extracranial carotid arteries. , 1997, The Journal of the Association of Physicians of India.

[33]  J. Grotta,et al.  Early stroke treatment associated with better outcome: the ninds rt-pa stroke study , 2000, Neurology.

[34]  E. Topol,et al.  Recognition of the importance of embolization in atherosclerotic vascular disease. , 2000, Circulation.

[35]  R. Califf,et al.  Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial. , 2000, Journal of the American College of Cardiology.

[36]  T Brott,et al.  Treatment of acute ischemic stroke. , 2000, The New England journal of medicine.

[37]  P. Armstrong,et al.  Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. , 2001 .

[38]  S. Ho,et al.  Intracarotid Abciximab Injection to Abort Impending Ischemic Stroke during Carotid Angioplasty , 2001, Cerebrovascular Diseases.

[39]  H. Pereira,et al.  Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial , 2001, The Lancet.

[40]  J. Grotta,et al.  Clinical Deterioration Following Improvement in the NINDS rt-PA Stroke Trial , 2001, Stroke.

[41]  Deepak L. Bhatt,et al.  Initial Experience of Platelet Glycoprotein IIb/IIIa Inhibition With Abciximab During Carotid Stenting: A Safe and Effective Adjunctive Therapy , 2001, Stroke.

[42]  R. Seitz,et al.  Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein IIb/IIIa inhibitor: report of four cases. , 2001, Radiology.

[43]  M. Chopp,et al.  Dynamic platelet accumulation at the site of the occluded middle cerebral artery and in downstream microvessels is associated with loss of microvascular integrity after embolic middle cerebral artery occlusion , 2001, Brain Research.

[44]  A. Alexandrov,et al.  Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator , 2002, Neurology.

[45]  G. Thomalla,et al.  Acute Basilar Artery Occlusion Treated With Combined Intravenous Abciximab and Intra-arterial Tissue Plasminogen Activator: Report of 3 Cases , 2002, Stroke.

[46]  R. Califf,et al.  The Abciximab ST-Recovery on AMI (ASTRONAMI) GUSTO V substudy: enhanced early speed, stability, and quality of reperfusion with anti-pletelet augmented thrombolytic therapy for ST-elevation AMI , 2002 .

[47]  Klaus Rasmussen,et al.  A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. , 2003, The New England journal of medicine.

[48]  M. Crouch,et al.  Glycoprotein IIb/IIIa Receptor Inhibitors in Percutaneous Coronary Intervention and Acute Coronary Syndrome , 2003, The Annals of pharmacotherapy.

[49]  Dong Ik Kim,et al.  Immediate reocclusion following a successful thrombolysis in acute stroke: A pilot study , 2003, Neurology.

[50]  M. Wholey,et al.  Evaluation of glycoprotein IIb/IIIa inhibitors in carotid angioplasty and stenting. , 2003, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[51]  R. Seitz,et al.  Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Stroke: Preliminary Observations , 2003, Stroke.

[52]  Zhenggang Zhang,et al.  Treatment of acute stroke with recombinant tissue plasminogen activator and abciximab. , 2003, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[53]  A. Qureshi,et al.  Safety of High-dose Intravenous Eptifibatide as an Adjunct to Internal Carotid Artery Angioplasty and Stent Placement: A Prospective Registry , 2004, Neurosurgery.

[54]  G. Proimos.  Platelet Aggregation Inhibition with Glycoprotein IIb–IIIa Inhibitors , 2001, Journal of Thrombosis and Thrombolysis.