Protective Effects of Tranexamic Acid on Clopidogrel Before Coronary Artery Bypass Grafting

Abstract

Excessive bleeding and transfusion increase morbidity and mortality in patients receiving coronary artery bypass grafting (CABG), especially in those exposed to antiplatelet agents. To evaluate the influence and interaction of clopidogrel bisulfate and tranexamic acid on bleeding and transfusion outcomes. A multicenter randomized and blinded trial. Seven medical centers across China. 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). Patients were randomized to receive tranexamic acid (10-mg/kg-1 bolus and 10-mg/kg-1/h-1 maintenance dose) or placebo. The primary outcomes included blood loss, major bleeding, and red blood cell (RBC) transfusion volume and exposure. 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. 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 REGISTRATIONL clinicaltrials.gov Identifier: NCT01060163.