Abciximab: an updated review of its therapeutic use in patients with ischaemic heart disease undergoing percutaneous coronary revascularisation.
Abciximab (Reopro) is an antibody fragment that dose-dependently inhibits platelet aggregation and leucocyte adhesion by binding to the glycoprotein (GP) IIb/IIIa, vitronectin and Mac-1 receptors. Abciximab (0.25 mg/kg bolus plus infusion of 0.125 micro g/kg/min for 12 hours) showed greater efficacy than tirofiban in reducing the 30-day composite endpoint of death, nonfatal myocardial infarction (MI) or urgent target-vessel revascularisation in the randomised, double-blind TARGET study in patients scheduled for stent placement. In addition, the beneficial effects of treatment with abciximab previously observed in the randomised, multicentre, placebo-controlled EPILOG and EPISTENT studies have been maintained to 1 year, with a significantly reduced incidence of ischaemic complications relative to placebo consistently observed across a range of subgroups including age, sex, bodyweight and indication for revascularisation. The incidence of the composite endpoint was reduced in patients presenting with acute MI of <48 hours' duration in comparison with either fibrinolytic therapy or stenting alone in the randomised STOPAMI and ADMIRAL trials, primarily because of a reduced requirement for urgent repeat revascularisation and reduced incidence of mortality. In the randomised, nonblind, multicentre CADILLAC trial in patients with acute myocardial infarction (MI), stenting alone was superior to percutaneous transluminal coronary angioplasty (PTCA) and stenting alone was not inferior to PTCA plus abciximab. Recent large randomised, multicentre studies (ASSENT-3 and GUSTO-V) have shown higher efficacy (on various ischaemic endpoints) of abciximab in combination with either a reduced dose of tenecteplase or reteplase compared with the fibrinolytic drug alone. TIMI grade 3 flow rates at 60 and 90 minutes in the TIMI-14 and SPEED trials were higher in patients who received abciximab in combination with either alteplase or reteplase than abciximab alone and were similar to that seen with the full-dose fibrinolytic alone. In the randomised, multicentre GUSTO IV-ACS study, no significant differences in any of the ischaemic endpoints at either 7 or 30 days in patients with acute coronary syndromes who were not scheduled to undergo early revascularisation (within 12 hours of end of infusion) were apparent between those who received abciximab (bolus and either 24- or 48-hour infusion) and those who received placebo in addition to aspirin and heparin. The most common adverse events associated with the use of abciximab are bleeding complications and thrombocytopenia, although the risk of major bleeding can be limited through adhering to current administration protocols. Treatment costs are generally higher in both stent plus abciximab and angioplasty plus abciximab groups than stent plus placebo, primarily because of the acquisition cost of abciximab. Abciximab appeared most cost beneficial in high-risk patients undergoing elective percutaneous coronary revascularisation; among lower risk patients, abciximab therapy has been associated with higher total in-hospital and 6-month medical costs than eptifibatide.


CONCLUSIONS
The GP IIb/IIIa receptor antagonist abciximab, when used with aspirin and heparin, has demonstrated efficacy in reducing the short- and long-term risk of ischaemic complications in patients with ischaemic heart disease undergoing percutaneous coronary intervention, when used with aspirin and heparin. High-risk patients (including those with diabetes mellitus) derive particular benefits from abciximab treatment. Abciximab remains an important therapeutic option for the prevention of complications in patients with ischaemic heart disease.
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Tim
T
Ibbotson
Jane K
JK
McGavin
Karen L
KL
Goa
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D016239:MEDLINE; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D009204:Myocardial Revascularization; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077284:Abciximab