title: Clopidogrel loading dose and bleeding outcomes in patients undergoing urgent coronary artery bypass grafting.
abstract: BACKGROUND
  Coronary artery bypass grafting (CABG) performed within 5 days of clopidogrel administration is associated with increased bleeding. The impact of clopidogrel loading dose is unknown. We examined the effect of clopidogrel loading dose on bleeding outcomes in patients undergoing urgent CABG.
  
  
  METHODS
  Clinical outcomes were examined retrospectively for 196 consecutive patients undergoing urgent CABG within 5 days of a clopidogrel loading dose between January 2003 and June 2009. Major bleeding was defined as a fall in hemoglobin > 5 g/dL, fatal or intracranial bleeding, or cardiac tamponade.
  
  
  RESULTS
  One hundred forty-eight patients received 300 mg and 48 patients received ≥ 600 mg clopidogrel loading. Patients were predominantly male (78%) with a mean age of 66 ± 10 years. Mean duration from clopidogrel loading to CABG was 3.0 ± 1.5 and 3.0 ± 1.6 days for the 300 and 600 mg loading doses, respectively. Major bleeding occurred in 47% of patients receiving 300 mg and 73% of patients receiving ≥ 600 mg clopidogrel loading (P = .002). Compared with 300 mg, patients receiving ≥ 600 mg had greater 24-hour chest tube output (391 ± 251 vs 536 ± 354 mL, P = .01), stayed longer in surgical intensive care (4.3 ± 4.1 vs 5.0 ± 3.1 days, P = .0001), and trended toward greater reoperation for bleeding (5% vs 12%, P = .09). Following multivariate analysis, clopidogrel loading dose ≥ 600 mg (odds ratio 2.8, CI 1.2-6.6), preoperative hemoglobin (3.4, 2.7-5.0 per 1 g/dL increase), and female gender (2.9, 1.1-7.4) predicted major bleeding.
  
  
  CONCLUSIONS
  Higher clopidogrel loading doses are associated with increased bleeding when administered within 5 days of CABG. The development of shorter-acting, reversible, oral antiplatelet agents may reduce perioperative bleeding in this population.
authors.affiliation: Victoria Heart Institute Foundation, Victoria, British Columbia, Canada. nick.cruden@ed.ac.uk
authors.forename: Nicholas L M
authors.initials: NL
authors.lastname: Cruden
authors.forename: Kristin
authors.initials: K
authors.lastname: Morch
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Wong
authors.forename: W Peter
authors.initials: WP
authors.lastname: Klinke
authors.forename: John
authors.initials: J
authors.lastname: Ofiesh
authors.forename: J David
authors.initials: JD
authors.lastname: Hilton
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D001026:Coronary Artery Bypass; D004638:Emergency Treatment; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine