Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication.
BACKGROUND
Abciximab, a monoclonal antibody fragment against the platelet receptor alphaIIb beta3 integrin, prevents platelet aggregation. A randomized, placebo-controlled study showed that abciximab improves outcomes for patients undergoing percutaneous coronary angioplasty at 30 days and at 6 months.


OBJECTIVE
To determine whether abciximab improves outcomes 3 years after coronary angioplasty.


METHODS
Double-blind, placebo-controlled, randomized trial.


METHODS
A total of 56 academic and community hospitals in the United States.


METHODS
A total of 2099 high-risk patients undergoing coronary angioplasty were randomized. Sufficient time elapsed for 2.5 years of follow-up among 2001 patients and for 3 years of follow-up among 1599 patients.


METHODS
Abciximab bolus of 0.25 mg/kg followed by infusion at 10 microg/min for 12 hours; abciximab bolus of 0.25 mg/kg followed by placebo infusion; or placebo bolus followed by placebo infusion.


METHODS
The primary outcome was the composite of death, myocardial infarction, or coronary revascularization. Secondary outcomes were death, myocardial infarction, or coronary revascularization individually. Subgroups having refractory unstable angina or evolving myocardial infarction and having different elevations of creatine kinase during initial angioplasty were analyzed.


RESULTS
At 3 years, composite end points occurred in 41.1% of those receiving abciximab bolus plus infusion; 47.4% of those receiving abciximab bolus only; and 47.2% of those receiving placebo only (for abciximab bolus plus infusion vs placebo, P=.009). Death occurred in 6.8%, 8.0%, and 8.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.20); myocardial infarction in 10.7%, 12.2%, and 13.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.08); and revascularization in 34.8%, 38.6%, and 40.1%, respectively (for abciximab bolus plus infusion vs placebo, P=.02). Among those with refractory unstable angina or evolving myocardial infarction, death occurred in 5.1%, 9.2%, and 12.7%, respectively (for abciximab bolus plus infusion vs placebo, P=.01). Death rates increased as periprocedural creatine kinase levels increased.


CONCLUSIONS
Abciximab bolus with infusion given at the time of coronary angioplasty improves outcomes as long as 3 years after the procedure.
Topol
E J
EJ
Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA. topole@cesmtp.ccf.org
Ferguson
J J
JJ
Weisman
H F
HF
Tcheng
J E
JE
Ellis
S G
SG
Kleiman
N S
NS
Ivanhoe
R J
RJ
Wang
A L
AL
Miller
D P
DP
Anderson
K M
KM
Califf
R M
RM
D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD; D003327:Coronary Disease / Q000628:therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D039661:Integrin beta3; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000517:prevention & control*; D009204:Myocardial Revascularization; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D010980:Platelet Membrane Glycoproteins; D016016:Proportional Hazards Models; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007140:Immunoglobulin Fab Fragments; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D019030:Receptors, Vitronectin; D000077284:Abciximab