title: Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention. EPIC Investigators.
abstract: BACKGROUND
  The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial.
  
  
  RESULTS
  Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P < .001). Most major bleeding complications occurred at the femoral access site, regardless of treatment. Intracranial hemorrhage (0.3%) and death (0.09%) attributable to major bleeding complications were rare. Multivariable regression analyses identified several variables significantly and independently related to major bleeding complications or greater blood loss, including greater age, female sex, lower weight, c7E3 Fab therapy, and duration and complexity of the index procedure. Major bleeding complications and blood loss in patients receiving bolus plus infusion were not significantly greater than in those receiving bolus alone (P = .38 and P = .14, respectively).
  
  
  CONCLUSIONS
  Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization.
authors.affiliation: Division of Cardiology, St. Louis University Health Sciences Center, MO 63110, USA.
authors.forename: F V
authors.initials: FV
authors.lastname: Aguirre
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
authors.forename: J J
authors.initials: JJ
authors.lastname: Ferguson
authors.forename: K
authors.initials: K
authors.lastname: Anderson
authors.forename: J C
authors.initials: JC
authors.lastname: Blankenship
authors.forename: R R
authors.initials: RR
authors.lastname: Heuser
authors.forename: K
authors.initials: K
authors.lastname: Sigmon
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.forename: R
authors.initials: R
authors.lastname: Gottlieb
authors.forename: G
authors.initials: G
authors.lastname: Hanovich
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000906:Antibodies / Q000009:adverse effects*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D016023:Integrins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000009:adverse effects; D012307:Risk Factors; D013927:Thrombosis / Q000517:prevention & control*; D014652:Vascular Diseases / Q000150:complications / Q000628:therapy*
chemical_list: D000906:Antibodies; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D011993:Recombinant Fusion Proteins