Protective Effects of Tranexamic Acid on Clopidogrel Before Coronary Artery Bypass Grafting A Multicenter Randomized Trial

Importance: Excessive bleeding and transfusion increase morbidity and mortality in patients receiving coronary artery bypass grafting (CABG), especially in those exposed to antiplatelet agents. Objective: To evaluate the influence and interaction of clopidogrel bisulfate and tranexamic acid on bleeding and transfusion outcomes. Design: A multicenter randomized and blinded trial. Setting: Seven medical centers across China. Participants: Patients eligible for randomization were 1173 men and women aged 18 to 85 years undergoing primary and isolated on-pump CABG; 570 adults were randomized and 552 were analyzed. Patients were recruited and stratified into 3 levels according to preoperative clopidogrel exposure (clopidogrel ingestion <= 7 days, clopidogrel discontinuation >7 days, and nonexposure). Intervention: Patients were randomized to receive tranexamic acid (10-mg/kg(-1) bolus and 10-mg/kg(-1)/h(-1) maintenance dose) or placebo. Main Outcome Measure: The primary outcomes included blood loss, major bleeding, and red blood cell (RBC) transfusion volume and exposure. Results: As compared with controls, clopidogrel increased blood loss (mean difference [MD], 270 mL; 95% CI, 135 to 404 mL), major bleeding (risk difference [RD], 18.5; 95% CI, 7.85 to 29.2), volume of RBCs transfused (MD, 2.97 U; 95% CI, 1.51 to 4.43 U), and RBC transfusion exposure (RD, 17.9; 95% CI, 8.51 to 27.2). As compared with placebo, tranexamic acid reduced blood loss (MD, -278 mL; 95% CI, -380 mL to -176 mL), major bleeding (RD, -19.5; 95% CI, -27.7 to -11.4), volume of RBCs transfused (MD, -2.58 U; 95% CI -3.61 U to -1.55 U), and RBC transfusion exposure (RD, -18.9; 95% CI, -26.4 to -11.4). Subgroup analysis demonstrated a significantly enhanced effect of tranexamic acid especially in patients with impaired platelet function. Conclusions and Relevance: Preoperative clopidogrel exposure increased bleeding and transfusion requirements in patients receiving on-pump CABG. Tranexamic acid reduced this risk and provided extra protection selectively in the patients with persistent clopidogrel exposure within 7 days before surgery. Trial Registration: clinicaltrials.gov Identifier: NCT01060163.