title: Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators.
abstract: Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months and, as yet, there is no known treatment to decrease this event. We tested a monoclonal antibody Fab fragment (c7E3) directed against the platelet glycoprotein IIb/IIIa integrin, the receptor mediating the final common pathway of platelet aggregation, to see whether it reduced the frequency of clinical restenosis. Patients who had unstable angina, recent or evolving myocardial infarction, or high-risk angiographic morphology, were randomised to receive c7E3 bolus and a 12 hour infusion of c7E3 (708 patients), c7E3 bolus and placebo infusion (695 patients), or placebo bolus and placebo infusion (696 patients). With maintenance of the double-blind state, patients were followed-up for at least 6 months to determine the need for repeat angioplasty or surgical coronary revascularisation and the occurrence of ischaemic events. By 30 days, 12.8% of placebo bolus/placebo infusion patients had had a major ischaemic event (death, myocardial infarction, urgent revascularisation), compared with 8.3% of c7E3 bolus/c7E3 infusion patients, yielding a 4.5% difference (35% reduction, p = 0.008). At 6 months, the absolute difference in patients with major ischaemic event or elective revascularisation was 8.1% between placebo bolus/placebo infusion and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction p = 0.001). The favourable long-term effect was mainly due to less need for bypass surgery or repeat angioplasty in patients with an initial successful procedure, since need for repeat target vessel revascularisation was 26% less for c7E3 bolus/c7E3 infusion than for placebo treatment (16.5% vs 22.3%; p = 0.007). The c7E3 bolus/placebo infusion group had an intermediate outcome which was not significantly better than that of the placebo bolus/placebo infusion group. These results extend the benefit of c7E3 bolus/c7E3 infusion from reducing abrupt closure and acute-phase adverse outcomes to a diminished need for subsequent coronary revascularisation procedures. Because this therapy carries a risk of bleeding complications and has been studied only in high-risk angioplasty patients, further evaluation is needed before it can be applied to other patient groups.
authors.affiliation: Department of Cardiology, Cleveland Clinic Foundation, OH 44195.
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
authors.forename: R M
authors.initials: RM
authors.lastname: Califf
authors.forename: H F
authors.initials: HF
authors.lastname: Weisman
authors.forename: S G
authors.initials: SG
authors.lastname: Ellis
authors.forename: J E
authors.initials: JE
authors.lastname: Tcheng
authors.forename: S
authors.initials: S
authors.lastname: Worley
authors.forename: R
authors.initials: R
authors.lastname: Ivanhoe
authors.forename: B S
authors.initials: BS
authors.lastname: George
authors.forename: D
authors.initials: D
authors.lastname: Fintel
authors.forename: M
authors.initials: M
authors.lastname: Weston
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017225:Atherectomy, Coronary / Q000009:adverse effects; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000401:mortality / Q000517:prevention & control / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D012008:Recurrence; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins