Abciximab

Abstract

Abciximab is a glycoprotein IIb/IIIa receptor antagonist that has proven to be of significant clinical value in improving patient outcome after percutaneous coronary revascularisation. Primarily, the drug inhibits platelet aggregation, but it may also have anticoagulant activity and other beneficial effects, such as inhibiting migration and promoting apoptosis of smooth muscle cells. Large well designed studies have found administration of abciximab (as an adjunct to heparin and aspirin) during percutaneous coronary revascularisation to significantly reduce the incidence of ischaemic complications occurring in the 30 days after the procedure. Significant benefit, particularly on the incidence of myocardial infarction, was still evident after 6 months in 2 of 4 major trials. Abciximab provides particular benefit in patients with unstable angina or myocardial infarction who are undergoing percutaneous coronary revascularisation. The benefits of the drug are additive to those achieved with coronary stenting. Very preliminary data suggest that abciximab may improve coronary blood flow after myocardial infarction and allow reperfusion to be achieved with reduced thrombolytic doses. Caution is required to minimise the risk of bleeding complications with the use of abciximab in combination with heparin and aspirin. Careful patient selection, use of an appropriate heparin regimen, early vascular sheath removal and meticulous femoral artery access site care are recommended. Thrombocytopenia can occur with abciximab treatment, but severe cases are uncommon (in vitro and ex vivo data indicate that abciximab has other pharmacological actions that may be of clinical relevance in preventing ischaemic events. The drug appears to weaken clot structure, have anticoagulant activity, inhibit migration and promote apoptosis of restenotic smooth muscle cells, and inhibit Mac-1-mediated adhesion of monocytes to fibrinogen and intercellular adhesion molecule-1. Because abciximab binds rapidly to platelets, it has a very short plasma half-life. However, platelet-bound drug is still detectable for several weeks after administration. Abciximab (0.25 mg/kg bolus plus infusion of 10 μg/min or 0.125 μg/kg/min) has been investigated as an adjunct to heparin and aspirin in patients undergoing percutaneous coronary revascularisation. Large well designed studies involving >9000 patients have shown that it prevents acute ischaemic complications [death, myocardial infarction (MI) or need for urgent intervention to treat recurrent ischaemia]. In the first pivotal trial of abciximab, which involved patients at high risk for ischaemic complications during percutaneous coronary revascularisation, abciximab (bolus plus infusion) had a significant effect, compared with placebo, in reducing the incidence of acute ischaemic complications in the first 30 days after the procedure (8.3% vs 12.8%; relative reduction 35%). Abciximab was particularly beneficial in the highest risk patients in this study (i.e. those with acute MI or unstable angina). The efficacy of abciximab was confirmed in subsequent studies, in which the drug significantly reduced the incidence of acute ischaemic complications in a general patient population undergoing percutaneous coronary revascularisation, excluding those with acute ischaemic syndromes (relative reduction approximately 55%), in patients with unstable angina undergoing percutaneous coronary revascularisation (relative reduction 29%) and in patients with acute MI undergoing primary percutaneous coronary revascularisation (relative reduction 48%). Most of the beneficial effect of abciximab in these studies was attributable to a reduction in the incidence of MI and/or the need for urgent revascularisation within 30 days after percutaneous coronary revascularisation. In the study in patients with unstable angina, abciximab appeared to stabilise plaques to some extent. The drug did not have a pronounced effect on mortality rates in any of the studies. A significantly lower incidence of ischaemic complications in abciximab-treated patients, compared with placebo recipients, was still evident at the 6-month follow-up...