Tranexamic Acid in Patients Undergoing Noncardiac Surgery

P. J. Devereaux*, Maura Marcucci, Thomas W. Painter, David Conen, Vladimir Lomivorotov, Daniel I. Sessler, Matthew T.V. Chan, Flavia K. Borges, María J. Martínez-Zapata, Chew Yin Wang, Denis Xavier, Sandra N. Ofori, Michael K. Wang, Sergey Efremov, Giovanni Landoni, Ydo V. Kleinlugtenbelt, Wojciech Szczeklik, Denis Schmartz, Amit X. Garg, Timothy G. ShortMaria Wittmann, Christian S. Meyhoff, Mohammed Amir, David Torres, Ameen Patel, Emmanuelle Duceppe, Kurt Ruetzler, Joel L. Parlow, Vikas Tandon, Edith Fleischmann, Carisi A. Polanczyk, Andre Lamy, Sergey V. Astrakov, Mangala Rao, William K.K. Wu, Keyur Bhatt, Miriam de Nadal, Valery V. Likhvantsev, Pilar Paniagua, Hector J. Aguado, Richard P. Whitlock, Michael H. McGillion, Michael Prystajecky, Jessica Vincent, John Eikelboom, Ingrid Copland, Kumar Balasubramanian, Alparslan Turan, Shrikant I. Bangdiwala, David Stillo, Peter L. Gross, Teresa Cafaro, Pascal Alfonsi, Pavel S. Roshanov, Emilie P. Belley-Côté, Jessica Spence, Toby Richards, Tomas VanHelder, William McIntyre, Gordon Guyatt, Salim Yusuf, Kate Leslie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 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; one-sided P=0.04 for noninferiority). CONCLUSIONS Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established.

Original languageEnglish
Pages (from-to)1996-1997
Number of pages2
JournalNew England Journal of Medicine
Volume386
Issue number21
DOIs
StatePublished - 26 May 2022

Bibliographical note

Funding Information:
Supported by a Foundation Grant (FDN-143302, to Dr. De-vereaux) from the Canadian Institutes of Health Research, a Project Grant (1162362) from the Australian National Health and Medical Research Council, and a grant from General Research Fund 14104419, Research Grant Council, Hong Kong, and by the Population Health Research Institute.

Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.

Fingerprint

Dive into the research topics of 'Tranexamic Acid in Patients Undergoing Noncardiac Surgery'. Together they form a unique fingerprint.

Cite this