Safety and Efficacy of Tranexamic Acid in General Surgery.

Abstract

Importance: Perioperative bleeding is common in general surgery. The POISE-3 (Perioperative Ischemic Evaluation-3) trial demonstrated efficacy of prophylactic tranexamic acid (TXA) compared with placebo in preventing major bleeding without increasing vascular outcomes in noncardiac surgery.

Objective: To determine the safety and efficacy of prophylactic TXA, specifically in general surgery.

Design, setting, and participants: Subgroup analyses were conducted that compared randomized treatment with TXA vs placebo according to whether patients underwent general surgery or nongeneral surgery in the POISE-3 blinded, international, multicenter randomized clinical trial. Participants were 45 years or older, were undergoing noncardiac surgery, had increased cardiovascular risk, and were expected to require at least an overnight hospital admission after surgery. Among 26 581 eligible patients identified, 17 046 were excluded, resulting in 9535 patients randomized to the POISE-3 trial. Participants were enrolled from June 2018 through July 2021. The data were analyzed during December 2023.

Intervention: Prophylactic, 1-g bolus of intravenous TXA or placebo at the start and end of surgery.

Main outcomes and measures: The primary efficacy outcome was a composite of life-threatening bleeding, major bleeding, or bleeding into a critical organ. The primary safety outcome was a composite of myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism at 30 days. Cox proportional hazards models were conducted, incorporating tests of interaction.

Results: Among 9535 POISE-3 participants, 3260 underwent a general surgery procedure. Mean age was 68.6 (SD, 9.6) years, 1740 were male (53.4%), and 1520 were female (46.6%). Among general surgery patients, 8.0% and 10.5% in the TXA and placebo groups, respectively, had the primary efficacy outcome (hazard ratio [HR], 0.74; 95% CI, 0.59-0.93; P = .01) and 11.9% and 12.5% in the TXA and placebo groups, respectively, had the primary safety outcome (HR, 0.95; 95% CI, 0.78-1.16; P = .63). There was no significant interaction by type of surgery (general surgery vs nongeneral surgery) on the primary efficacy (P for interaction = .81) and safety (P for interaction = .37) outcomes. Across subtypes of general surgery, TXA decreased the composite bleeding outcome in hepatopancreaticobiliary surgery (HR, 0.55; 95% CI, 0.34-0.91 [n = 332]) and colorectal surgery (HR, 0.67; 95% CI, 0.45-0.98 [n = 940]). There was no significant interaction across subtypes of general surgery (P for interaction = .68).

Conclusions and relevance: In this study, TXA significantly reduced the risk of perioperative bleeding without increasing cardiovascular risk in patients undergoing general surgery procedures.

Trial registration: ClinicalTrials.gov Identifier: NCT03505723.