Clinical experience with abciximab during coronary revascularisation: an overview.
Despite improvements in the safety and efficacy of percutaneous transluminal coronary angioplasty (PTCA), ischaemic procedural complications continue to occur in up to 10 to 20% of patients. As the pivotal role of platelets in the formation of arterial thrombosis following coronary intervention was elucidated, it became apparent that an inhibitor of platelet aggregation might reduce the rate of acute ischaemic complications and restenosis following PTCA. Attention has focused on the platelet glycoprotein (GP) IIb/IIIa integrin, a receptor that mediates the final common pathway of platelet aggregation. A murine monoclonal antibody that binds to and blocks the IIb/IIIa receptor inhibits the binding of fibrinogen to platelets and thus inhibits platelet aggregation. To minimise the potential for human anti-murine antibody responses, this antibody was modified to a chimaeric antibody fragment, abciximab (c7E3 Fab), composed of an antigen-binding fragment with human constant regions and mouse variable regions. Abciximab was recently approved by the US Food and Drug Administration for clinical use. The efficacy and safety of abciximab have been demonstrated in 3 recently completed phase III clinical trials which enrolled a total of 6156 patients undergoing coronary angioplasty. The study results have unequivocally demonstrated that platelet GP IIb/IIIa receptor inhibition with abciximab during coronary intervention markedly reduces the incidence of postprocedural ischaemic events. In the EPIC trial, a dose-related effect of abciximab in the prevention of ischaemic complications was observed, with a significant 35% reduction in the incidence of the composite end-point among the patients receiving the abciximab bolus and 12-hour infusion compared with the double-placebo group. In the EPILOG trial, patients treated with abciximab bolus and 12-hour infusion with low-dose heparin had a significant 56% reduction in the incidence of the composite end-point at 30 days. In the CAPTURE study, the primary end-point was reduced at 30 days by 29% with abciximab therapy. The treatment effect observed at 30 days for reduction in acute ischaemic complication was maintained throughout the 6-month follow-up period. Although abciximab therapy may carry an increased risk of bleeding complications, such excess haemorrhagic risk can be eliminated by strategies such as reduction of adjunctive heparin dosage, early sheath removal, and conservative management of the vascular access site. The role of platelet glycoprotein IIb/IIIa receptor inhibition in the acute coronary syndromes of unstable angina and acute myocardial infarction treated by percutaneous intervention or with thrombolytic therapy is an exciting new frontier in ischaemic heart disease and is currently under investigation. The complementarity of these agents with new devices for coronary revascularisation, such as stents, is also the subject of important new trials. Finally, future studies will also focus on the role of long term GP IIb/IIIa inhibition with the new generation of orally active agents.
Guetta
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Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Lincoff
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