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, POISE-3 Investigators, Marlene Søgaard (Member of study group), Ossian Gundel (Member of study group), Viktor Moseholm (Member of study group), Diana B. Jensen (Member of study group), Mia K Hansen (Member of study group), Grethe Bendixen (Member of study group), Anne Sofie Jensen (Member of study group), Sanne Dahl Thorsager Olesen (Member of study group), Naomi Nadler (Member of study group), Mette Krogh Østerby (Member of study group), Mojgan Vazin Kjeldsen (Member of study group), Jawad Ahmad Zahid (Member of study group), Nessn Azawi (Member of study group), Ismail Gögenur (Member of study group), Eske Kvanner Aasvang (Member of study group), Niels Brandt Højlund-Hansen (Member of study group), Theis Simon Bak (Member of study group), Thomas Kistorp (Member of study group), Martin Andreas Røder (Member of study group)


BACKGROUND: 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. (Funded by the Canadian Institutes of Health Research and others; POISE-3 number, NCT03505723.).

Original languageEnglish
JournalThe New England journal of medicine
Issue number21
Pages (from-to)1986-1997
Number of pages12
Publication statusPublished - 26 May 2022


  • Antifibrinolytic Agents/adverse effects
  • Canada
  • Hemorrhage/etiology
  • Humans
  • Surgical Procedures, Operative
  • Thrombosis/chemically induced
  • Tranexamic Acid/adverse effects


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