title: Lack of clopidogrel pretreatment effect on the relative efficacy of bivalirudin with provisional glycoprotein IIb/IIIa blockade compared to heparin with routine glycoprotein IIb/IIIa blockade: a REPLACE-2 substudy.
abstract: OBJECTIVE
  The purpose of this study was to assess if clopidogrel pretreatment affects the relative efficacy of bivalirudin versus heparin with glycoprotein (GP) IIb/IIIa blockade for percutaneous coronary interventions (PCI).
  
  
  BACKGROUND
  Although thienopyridine pretreatment may improve clinical outcomes with PCI, it is unknown if bivalirudin's efficacy compared with heparin is dependent upon such pretreatment.
  
  
  METHODS
  The Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to reduced Clinical Events (REPLACE-2) trial was a double-blind, triple-dummy, randomized-controlled trial comparing heparin plus routine GP IIb/IIIa blockade (heparin group) with bivalirudin plus provisional GP IIb/IIIa blockade (bivalirudin group) during PCI. The primary end point was a composite of death, myocardial infarction (MI), urgent revascularization at 30 days, and major in-hospital bleeding. The secondary end point was a 30-day composite of death, MI, and urgent revascularization. Clopidogrel pretreatment was encouraged (300 mg loading, 75 mg/day).
  
  
  RESULTS
  Of 6,010 patients enrolled, 5,893 received clopidogrel, with 85.8% in the bivalirudin and 84.6% in the heparin group receiving clopidogrel pretreatment. Bivalirudin (provisional GP IIb/IIIa blockade 7.2%) was noninferior to the heparin group for both primary and secondary end points. Clopidogrel pretreatment did not affect the relative efficacy of bivalirudin versus heparin with GP IIb/IIIa blockade, irrespective of pretreatment duration. Pretreatment was associated with significantly lower primary end point with bivalirudin (8.7% pretreatment vs. 12.9% no pretreatment, p = 0.007), and nonsignificantly with heparin (9.7% vs. 11.7%, respectively, p = 0.20). Multivariable models showed a trend toward lower primary and secondary end points with clopidogrel pretreatment.
  
  
  CONCLUSIONS
  Clopidogrel pretreatment at the doses and time administered in this trial did not influence the relative efficacy of bivalirudin versus heparin plus GP IIb/IIIa blockade for PCI. However, pretreatment was associated with a trend towards lower clinical events after PCI.
authors.affiliation: Department of Cardiovascular Medicine, the Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Saw
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Walter
authors.initials: W
authors.lastname: DeSmet
authors.forename: Amadeo
authors.initials: A
authors.lastname: Betriu
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rutsch
authors.forename: Robert G
authors.initials: RG
authors.lastname: Wilcox
authors.forename: Neil S
authors.initials: NS
authors.lastname: Kleiman
authors.forename: Kathy
authors.initials: K
authors.lastname: Wolski
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D003327:Coronary Disease / Q000628:therapy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; C074619:bivalirudin