Tranexamic Acid For the Prevention of Perioperative Bleeding

Perioperative bleeding is a key complication associated with increased morbidity and mortality.1 Due to an aging population worldwide, the bleeding and thrombotic risk of patients undergoing noncardiac surgery is increasing.2 Tranexamic acid is an antifibrinolytic drug3 that has been shown in large clinical trials to decrease the incidence and severity of bleeding during cesarean section and cardiac surgery.4,5 Small clinical trials suggest that it may decrease bleeding in orthopedic surgery6 but there is limited data on its use in noncardiac, non-orthopedic surgery.7 The Perioperative Ischemic Evaluation–3 (POISE-3)8 investigators examined the use of tranexamic acid administered at the start and end of noncardiac surgery for the prevention of bleeding events in patients judged to be at increased cardiovascular (CV) risk. The study also evaluated a hypotension- versus hypertension-avoidance strategy, which will not be discussed here.

The primary efficacy outcome of the POISE-3 trial was a composite of life-threatening bleeding, major bleeding, or bleeding into a critical organ at 30 days. The primary safety outcome was a composite CV outcome at 30 days, including myocardial injury, non-hemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism. In this randomized, international trial of 9,535 patients, the incidence of the composite bleeding outcome was 24% lower with tranexamic acid than with placebo (9.1% vs. 11.7%; absolute difference, −2.6 percentage points; 95% confidence interval [CI], −3.8 to −1.4). Noninferiority was not met for a composite CV outcome event which occurred in 14.2% of the patients in the tranexamic acid group and 13.9% of those in the placebo group (hazard ratio [HR], 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, −1.1 to 1.7). The inability of the study to demonstrate noninferiority of the composite safety endpoint despite similar incidence of events may have been related to the narrow noninferiority margin chosen.

This large randomized controlled trial provides evidence that transexamic acid is an effective agent for the reduction of clinically significant perioperative bleeding in noncardiac surgery, but the outcome is tempered by a possible increase in CV outcomes. The use of tranexamic acid should remain individualized, with probable benefit in those at high risk for bleeding and lower risk for CV outcomes. Safety will need to be confirmed before its use becomes standardized in a broader group of patients, particularly those at higher risk for perioperative CV outcomes.


  1. Smilowitz NR, Oberweis BS, Nukala S, et al. Association between anemia, bleeding, and transfusion with long-term mortality following non-cardiac surgery. Am J Med 2016;129:315-23.e2
  2. Smilowitz NR, Gupta N, Guo Y, Beckman JA, Bangalore S, Berger JS. Trends in cardiovascular risk factor and disease prevalence in patients undergoing non-cardiac surgery. Heart 2018;104:1180-86.
  3. Sperzel M, Huetter J. Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost 2007;5:2113-18.
  4. Sentilhes L, Senat MV, Le Lous M, et al. Tranexamic acid for the prevention of blood loss after cesarean delivery. N Engl J Med 2021;384:1623-34.
  5. Myles PS, Smith JA, Forbes A, et al. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med 2017;376:136-48.
  6. Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res 2009;123:687-96.
  7. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012;344:e3054.
  8. Devereaux PJ, Marcucci M, Panter TW, et al. Tranexamic acid in patients undergoing noncardiac surgery. N Engl J Med 2022;386:1986-97.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Interventions and Vascular Medicine, Hypertension

Keywords: ACC22, ACC Annual Scientific Session, Antifibrinolytic Agents, Tranexamic Acid, Cesarean Section, Confidence Intervals, Pregnancy, Incidence, Venous Thromboembolism, Hemorrhage, Cardiac Surgical Procedures, Hypertension, Hypotension, Thrombosis

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