Benefits and risks of using clopidogrel before coronary artery bypass surgery: systematic review and meta-analysis of randomized trials and observational studies

J Thorac Cardiovasc Surg. 2012 Mar;143(3):665-675.e4. doi: 10.1016/j.jtcvs.2011.01.069. Epub 2011 Jun 24.


Objective: The benefits and risks associated with the use of clopidogrel before coronary artery bypass grafting are controversial, and these were investigated in the present meta-analysis.

Methods: A systematic literature search was performed to identify studies on the use of clopidogrel before coronary artery bypass grafting. Meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews.

Results: The literature search yielded 3 prospective randomized studies and 17 observational studies with valid data. Randomized studies were post hoc analyses of the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY), Clopidogrel for the Reduction of Events During Observation (CREDO), and Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events trials. Meta-analysis based on these data showed a nonsignificant reduced risk of immediate postoperative composite end point (death, myocardial infarction, or stroke) in the clopidogrel group (risk ratio [RR], 0.77; 95% confidence interval [CI], 0.58-1.04). Data from the CREDO and CLARITY trials showed a similar risk of death (RR, 0.81; 95% CI, 0.20-3.37), myocardial infarction (RR, 0.58; 95% CI, 0.25-1.33), and major bleeding according to Thrombolysis in Myocardial Infarction criteria (RR, 1.48; 95% CI, 0.72-3.04). Meta-analysis of observational studies showed that preoperative exposure to clopidogrel was associated with an increased risk of death (RR, 1.30; 95% CI, 1.02-1.67), reoperation for bleeding (RR, 1.88; 95% CI, 1.37-2.58), blood loss (mean difference, 157.8 mL; 95% CI, 61.9-253.6), need of packed red blood cell transfusion (RR, 1.23; 95% CI, 1.10-1.37), and increased use of blood products. A significantly reduced risk of postoperative myocardial infarction was observed among patients taking clopidogrel (RR, 0.63; 95% CI, 0.48-0.82).

Conclusions: Contrary to the findings of post hoc analyses of randomized trials, observational studies showed that recent exposure to clopidogrel before coronary artery bypass grafting is associated with increased risk of postoperative death, reoperations for bleeding, blood loss, and need of blood transfusions.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Blood Transfusion
  • Clinical Trials as Topic
  • Clopidogrel
  • Coronary Artery Bypass* / adverse effects
  • Coronary Artery Bypass* / mortality
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / surgery*
  • Drug Administration Schedule
  • Evidence-Based Medicine
  • Hemorrhage / chemically induced
  • Hemorrhage / therapy
  • Humans
  • Myocardial Infarction / etiology
  • Myocardial Infarction / prevention & control*
  • Patient Selection
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Reoperation
  • Risk Assessment
  • Risk Factors
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine