The anti-GPIIb-IIIa agents: fundamental and clinical aspects.
The platelet GPIIb/IIIa receptor mediates platelet aggregation induced by all physiologic agonists. Blockade of the receptor, either by monoclonal antibodies or small molecules patterned after the arginine glycine-aspartic acid (RGD) cell recognition domain, prevents arterial thrombosis in animal models much better than does aspirin. c7E3 Fab, the Fab fragment of the mouse/human chimeric antibody 7E3 (abciximab: ReoPro), was shown to reduce ischemic events after angioplasty when given in conjunction with heparin and aspirin to patients at high risk in the EPIC study, but its was associated with an increase in bleeding. Preliminary data from the subsequent EPILOG study, in which a lower dose of heparin was used, demonstrated efficacy in low risk as well as high risk patients and no significant increase in major bleeding. Preliminary data from the CAPTURE study support the use of c7E3 Fab in patients with unstable angina who are candidates for PTCA within 24 hours. Positive trends toward decreased thrombotic events have also been observed in patients treated with small molecule inhibitors of GPIIb/IIIa receptors. This new class of agents thus holds promise for improving the therapy of angioplasty as well as perhaps other thrombotic phenomena.
Coller
B S
BS
Mount Sinai School of Medicine, New-York, NY 10128, USA.
Anderson
K M
KM
Weisman
H F
HF
D000077284:Abciximab; D000789:Angina, Unstable / Q000188:drug therapy / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D004353:Drug Evaluation, Preclinical; D000077542:Eptifibatide; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D015337:Multicenter Studies as Topic; D009842:Oligopeptides / Q000276:immunology / Q000502:physiology; D010455:Peptides / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; C047981:arginyl-glycyl-aspartic acid; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab