title: Influence of timing of clopidogrel treatment on the efficacy and safety of bivalirudin in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention: an analysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.
abstract: OBJECTIVE
  This study sought to determine if the efficacy of bivalirudin alone versus heparin plus a glycoprotein (GP) IIb/IIIa inhibitor is dependent upon the duration of clopidogrel pre-treatment in patients undergoing percutaneous coronary intervention (PCI) in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.
  
  
  BACKGROUND
  The administration of a clopidogrel loading dose several hours before PCI reduces the risk of periprocedural thrombotic events.
  
  
  METHODS
  Patients with an acute coronary syndrome were randomized to heparin plus a GP IIb/IIIa inhibitor (control), bivalirudin plus a GP IIb/IIIa inhibitor, or bivalirudin alone. Dose and timing of clopidogrel were left to the investigator's discretion.
  
  
  RESULTS
  Of 13,819 patients randomized, 7,789 underwent PCI. When clopidogrel was initiated at any time before angiography or within 30 min after PCI, randomization to bivalirudin alone (n = 2,284) or control (n = 2,189) was associated with similar ischemic outcomes (8.2% vs. 8.3%, risk ratio: 0.98, 95% confidence interval: 0.81 to 1.20). Those patients who received clopidogrel >30 min after PCI or not at all experienced an increase in ischemic events when randomized to bivalirudin alone (n = 290) versus control (n = 317) (14.1% vs. 8.5%, risk ratio: 1.66, 95% confidence interval: 1.05 to 2.63). Major bleeding was significantly less frequent in patients treated with bivalirudin alone.
  
  
  CONCLUSIONS
  This post-hoc analysis suggests that in acute coronary syndrome patients, as long as clopidogrel is administered before or within 30 min of PCI treatment with bivalirudin alone is similarly effective to heparin plus a GP IIb/IIIa inhibitor in suppressing 30-day ischemic events with significantly less bleeding. If it is anticipated that clopidogrel will be given late or not at all after PCI, bivalirudin alone may be associated with worse ischemic outcomes. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158).
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. lincofa@ccf.org
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: Steven V
authors.initials: SV
authors.lastname: Manoukian
authors.forename: Derek
authors.initials: D
authors.lastname: Chew
authors.forename: Charles V
authors.initials: CV
authors.lastname: Pollack
authors.forename: Frederick
authors.initials: F
authors.lastname: Feit
authors.forename: James H
authors.initials: JH
authors.lastname: Ware
authors.forename: Michel E
authors.initials: ME
authors.lastname: Bertrand
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.forename: Walter
authors.initials: W
authors.lastname: Desmet
authors.forename: David A
authors.initials: DA
authors.lastname: Cox
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000401:mortality; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000077144:Clopidogrel; D017023:Coronary Angiography; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D014336:Troponin / Q000097:blood; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D014336:Troponin; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; C074619:bivalirudin