New antiplatelet agents: platelet GPIIb/IIIa antagonists.
The GPIIb/IIIa (alpha IIb beta 3) receptor plays a crucial role in platelet aggregation and platelet thrombus formation. Inhibition of GPIIb/IIIa with the Fab fragment of the mouse/human chimeric monoclonal antibody 7E3, snake venom peptides containing the arginine-glycine-aspartic acid (RGD) sequence, or peptides or peptidomimetics based on the RGD sequence results in abolition of platelet aggregation and platelet thrombus formation. This results in profound inhibition of thrombotic occlusions in animal models. The Phase III EPIC study demonstrated that c7E3 Fab, given as bolus followed by a 12 h infusion, reduced the risk of acute ischemic complications after coronary angioplasty by approximately 35% in patients at high risk of suffering such complications. Treated patients had an approximately 2-fold increased risk of major bleeding, but no increase in cerebral hemorrhage or lethal bleeding. Treatment with c7E3 Fab may have had a beneficial effect on clinical restenosis at 6 months, but this needs to be confirmed. A possible anticoagulant effect of c7E3 Fab was also identified in EPIC, and in vitro studies support this possibility. With the approval of c7E3 Fab (abciximab; ReoPro) for patients undergoing high-risk angioplasty in the US and several European and Scandinavian countries, GPIIb/IIIa inhibition joins the armamentarium of antithrombotic agents.
Coller
B S
BS
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Anderson
K
K
Weisman
H F
HF
D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D002561:Cerebrovascular Disorders / Q000517:prevention & control; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology / Q000627:therapeutic use; D016023:Integrins / Q000378:metabolism; D015993:Life Tables; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D012910:Snake Venoms / Q000494:pharmacology / Q000627:therapeutic use; D013927:Thrombosis / Q000503:physiopathology / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D016023:Integrins; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012910:Snake Venoms; C047981:arginyl-glycyl-aspartic acid; D001241:Aspirin; D000077284:Abciximab