Tranexamic acid lowers bleeding in patients undergoing noncardiac surgery: NEJM

Australia: In a new study conducted by P.J. Devereaux and the team, it was found that the composite bleeding result was considerably lower with tranexamic acid compared with placebo in individuals undergoing noncardiac surgery. The findings of this study were published in The New England Journal of Medicine on 2nd April 2022.

Patients undergoing noncardiac surgery frequently have perioperative bleeding. Tranexamic acid is an antifibrinolytic medication that can be used to safely reduce such bleeding. As a result, this investigation was carried out as a clinical trial with patients receiving noncardiac surgery.

Patients were randomly put into groups to receive placebo or tranexamic acid (1-g intravenous bolus) at the start and end of surgery (described here), as well as a hypotension-avoidance or hypertension-avoidance approach using a partial factorial design. At 30 days, the key efficacy outcome was life-threatening hemorrhage, significant bleeding, or bleeding into a vital organ. Myocardial damage following noncardiac surgery, peripheral arterial thrombosis, non-hemorrhagic stroke, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) were the key safety outcomes at 30 days. To demonstrate tranexamic acid's noninferiority to placebo for the composite cardiovascular outcome, the upper limit of the one-sided 97.5 percent confidence interval for the hazard ratio had to be less than 1.125, and the one-sided P value had to be less than 0.025.

The results of this study stated as follow:

1. A total of 9535 patients were randomly assigned.

2. A composite bleeding outcome event occurred in 433 of 4757 tranexamic acid patients (9.1%) and 561 of 4778 placebo patients (11.7%) (hazard ratio, 0.76; absolute difference, 2.6% points).

3. A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) receiving tranexamic acid and 639 of 4601 patients (13.9%) receiving placebo (hazard ratio, 1.02; absolute difference, 0.3% points).

In conclusion, even though the difference between groups in the composite cardiovascular outcome was minor, tranexamic acid's noninferiority was not demonstrated.

Reference:

Devereaux, P. J., Marcucci, M., Painter, T. W., Conen, D., Lomivorotov, V., Sessler, D. I., Chan, M. T. V., Borges, F. K., Martínez-Zapata, M. J., Wang, C.-Y., Xavier, D., Ofori, S. N., Wang, M. K., Efremov, S., Landoni, G., Kleinlugtenbelt, Y. V., Szczeklik, W., Schmartz, D., Garg, A. X., … Leslie, K. (2022). Tranexamic Acid in Patients Undergoing Noncardiac Surgery. In New England Journal of Medicine. Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2201171

Keywords: Tranexamic acid, surgery, hemorrhage, venous thromboembolism, arterial thrombosis, cardiovascular, bleeding, NEJM, noncardiac