Clinical trials with glycoprotein IIB/IIIA antagonists - No benefit without bleeding?

As the glycoprotein GPIIb/IIIa receptor is the final common pathway in plat elet aggregation, antagonists of this receptor cause a profound inhibition of aggregation induced by any agonist. The short-term efficacy and safety o f GPIIb/IIIa antagonists in patients undergoing coronary angioplasty was de monstrated with murine 7E3 Fab, but this antibody was immunogenic. Abcixima b is a chimeric human-mouse monoclonal antibody that is less immunogenic. T he first major trial with a GPIIb/IIIa antagonist was the EPIC trial with a bciximab, which showed that abciximab reduced the ischemic complications of coronary balloon angioplasty and atherectomy in high-risk patients, but in creased the risk of bleeding. Subsequent studies showed that using less con current heparin reduced bleeding. Abciximab also reduced the rate of revasc ularization. Further studies have shown that the benefits of abciximab exte nded to all patients undergoing angioplasty (EPILOG), including patients wi th unstable angina (CAPTURE) and acute myocardial infarction (RAPPORT). Cli nical trials with eptifibatide and tirofiban have failed to demonstrate ben efit, at the doses used, in angioplasty. Abciximab and eptifibatide, but no t oral xemilofiban, improve the safety of the coronary stenting procedure. Shortterm intravenous treatment with lamifiban, eptifibatide or tirofiban i s beneficial in acute coronary syndromes (unstable angina, non-Q wave myoca rdial infarction). Orally active GPIIb/IIIa antagonists are being developed for use in acute coronary syndromes and myocardial infarction. However, no benefit has been shown with lefradafiban in acute coronary syndromes and s ibrafiban and orbofiban are harmful. Eptifibatide, lamifiban and abciximab improve coronary patency in myocardial infarction, and long-term trials of GPIIb/IIIa antagonists are being conducted in acute myocardial infarction. Abciximab can cause thrombocytopenia, and all the GPIIb/IIIa antagonists in crease the incidence of bleeding, but there is no excess of intracranial he morrhage. (C) 2001 Prous Science. All rights reserved.