This article is available to subscribers. Subscribe now. Already have an account? Sign in

Original ArticleFree Preview

Tranexamic Acid in Patients Undergoing Noncardiac Surgery

List of authors.
  • P.J. Devereaux, M.D., Ph.D.,
  • Maura Marcucci, M.D.,
  • Thomas W. Painter, M.B., Ch.B.,
  • David Conen, M.D., M.P.H.,
  • Vladimir Lomivorotov, M.D.,
  • Daniel I. Sessler, M.D.,
  • Matthew T.V. Chan, M.B., B.S., Ph.D.,
  • Flavia K. Borges, M.D., Ph.D.,
  • María J. Martínez-Zapata, M.D., Ph.D.,
  • Chew Yin Wang, M.B., Ch.B.,
  • Denis Xavier, M.D.,
  • Sandra N. Ofori, F.W.A.C.P.,
  • Michael K. Wang, M.D.,
  • Sergey Efremov, M.D., Ph.D.,
  • Giovanni Landoni, M.D.,
  • Ydo V. Kleinlugtenbelt, M.D., Ph.D.,
  • Wojciech Szczeklik, M.D., Ph.D.,
  • Denis Schmartz, M.D.,
  • Amit X. Garg, M.D., Ph.D.,
  • Timothy G. Short, M.B., Ch.B., M.D.,
  • Maria Wittmann, M.D.,
  • Christian S. Meyhoff, M.D., Ph.D.,
  • Mohammed Amir, F.R.C.S.Ed.,
  • David Torres, M.D.,
  • Ameen Patel, M.D., M.A.C.P.,
  • Emmanuelle Duceppe, M.D., Ph.D.,
  • Kurt Ruetzler, M.D., Ph.D.,
  • Joel L. Parlow, M.D.,
  • Vikas Tandon, M.D.,
  • Edith Fleischmann, M.D.,
  • Carisi A. Polanczyk, M.D., Sc.D.,
  • Andre Lamy, M.D.,
  • Sergey V. Astrakov, M.D., Ph.D.,
  • Mangala Rao, M.D.,
  • William K.K. Wu, Ph.D.,
  • Keyur Bhatt, M.S.,
  • Miriam de Nadal, M.D., Ph.D.,
  • Valery V. Likhvantsev, M.D.,
  • Pilar Paniagua, M.D., Ph.D.,
  • Hector J. Aguado, M.D., Ph.D.,
  • Richard P. Whitlock, M.D., Ph.D.,
  • Michael H. McGillion, R.N., Ph.D.,
  • Michael Prystajecky, M.D.,
  • Jessica Vincent, M.Sc.,
  • John Eikelboom, M.B., B.S.,
  • Ingrid Copland,
  • Kumar Balasubramanian, M.Sc.,
  • Alparslan Turan, M.D.,
  • Shrikant I. Bangdiwala, Ph.D.,
  • David Stillo, M.A.Sc.,
  • Peter L. Gross, M.D.,
  • Teresa Cafaro, M.D.,
  • Pascal Alfonsi, M.D., Ph.D.,
  • Pavel S. Roshanov, M.D.,
  • Emilie P. Belley-Côté, M.D., Ph.D.,
  • Jessica Spence, M.D., Ph.D.,
  • Toby Richards, M.D.,
  • Tomas VanHelder, M.D., Ph.D.,
  • William McIntyre, M.D., Ph.D.,
  • Gordon Guyatt, M.D.,
  • Salim Yusuf, M.D., D.Phil.,
  • and Kate Leslie, M.D.
  • for the POISE-3 Investigators*



Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding.


Download a PDF of the Research Summary.

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.


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).


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.)

Digital Object ThumbnailQUICK TAKE VIDEO SUMMARY
Tranexamic Acid in Noncardiac Surgery

Continue reading this article

Select an option below:

Create your account to get 2 free subscriber-only articles each month.

Get Free Access Now Subscribe For Full Access

Already have an account?

Sign In

Print subscriber?

Activate your online access.

Funding and Disclosures

Supported by a Foundation Grant (FDN-143302, to Dr. Devereaux) 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.

Disclosure forms provided by the authors are available with the full text of this article at

This article was published on April 2, 2022, at

A data sharing statement provided by the authors is available with the full text of this article at

Author Affiliations

From the Population Health Research Institute (P.J.D., M.M., D.C., F.K.B., S.N.O., M.K.W., A.L., R.P.W., M.H.M., J.V., J.E., I.C., K. Balasubramanian, S.I.B., D. Stillo, T.C., P.S.R., E.P.B.-C., J.S., W.M., S.Y.), the Departments of Health Research Methods, Evidence, and Impact (P.J.D., M.M., D.C., F.K.B., S.N.O., M.K.W., A.X.G., S.I.B., J.S., G.G.), Medicine (P.J.D., M.M., D.C., F.K.B., M.K.W., A.P., V.T., J.E., P.L.G., E.P.B.-C., W.M., G.G., S.Y.), Surgery (A.L., R.P.W.), and Anesthesia (J.S., T.V.) and the School of Nursing (M.H.M.), McMaster University, Hamilton, the Departments of Medicine (A.X.G., P.S.R.) and Epidemiology and Biostatistics (A.X.G.), Western University, London, and the Department of Anesthesiology and Perioperative Medicine, Queen’s University and Kingston Health Sciences Centre, Kingston (J.L.P.), ON, the Department of Medicine, Centre Hospitalier de l’Université de Montréal (E.D.), and the Department of Medicine, Jewish General Hospital, McGill University (T.C.), Montreal, and the Department of Medicine, University of Saskatchewan, Saskatoon (M.P.) — all in Canada; the Discipline of Acute Care Medicine, University of Adelaide (T.W.P.), and the Department of Anaesthesia, Royal Adelaide Hospital (T.W.P.), Adelaide, SA, and the Department of Anaesthesia and Perioperative Medicine, Monash University (T.R.), and the Department of Critical Care Medicine, Melbourne Medical School, University of Melbourne (K.L.), Melbourne, VIC — all in Australia; the Department of Anesthesiology and Intensive Care, E. Meshalkin National Medical Research Center (V.L.), and the Department of Anesthesiology and Intensive Care (V.L.) and the Department of Anesthesiology, V. Zelman Institute of Medicine and Psychology (S.V.A.), Novosibirsk State University, Novosibirsk, Saint Petersburg State University Hospital, Saint Petersburg (S.E.), and V. Negovsky Reanimatology Research Institute, Anesthesia and Intensive Care Department, First Moscow State Medical University (Sechenov University), Moscow (V.V.L.) — all in Russia; the Departments of Outcomes Research (D.I.S., K.R., A.T.) and General Anesthesia (K.R., A.T.) and the Anesthesiology Institute (D.I.S., K.R., A.T.), Cleveland Clinic, Cleveland; Chinese University of Hong Kong, Shatin, China (M.T.V.C., W.K.K.W.); Iberoamerican Cochrane Center, Public Health and Clinical Epidemiology Service, Institut d’Investigació Biomèdica Sant Pau, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (M.J.M.-Z.), the Department of Anesthesiology and Intensive Care, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona (M.N.), and the Anesthesiology Department, Santa Creu i Sant Pau University Hospital (P.P.), Barcelona, and the Trauma and Orthopedic Surgery Department, Hospital Clínico Universitario de Valladolid, Valladolid (H.J.A.) — all in Spain; the Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia (C.Y.W.); St. John’s Medical College, Bangalore (D.X., M.R.), and the Department of Gastrointestinal Surgery, Surat Institute of Digestive Sciences Hospital and Research Center, Surat (K. Bhatt) — both in India; the Department of Anesthesiology and Intensive Care, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan (G.L.); the Department of Orthopedic and Trauma Surgery, Deventer Ziekenhuis, Deventer, the Netherlands (Y.V.K.); Jagiellonian University Medical College, Center for Intensive Care and Perioperative Medicine, Krakow, Poland (W.S.); Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles, Brussels (D. Schmartz); the Department of Anesthesia, Auckland City Hospital, and the School of Health Sciences, University of Auckland, Auckland, New Zealand (T.G.S.); the Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany (M.W.); the Department of Anesthesia and Intensive Care, Copenhagen University Hospital–Bispebjerg and Frederiksberg, and the Department of Clinical Medicine, University of Copenhagen, Copenhagen (C.S.M.); Shifa International Hospital, Islamabad, Pakistan (M.A.); Departamento de Epidemiología y Estudios en Salud, Universidad de Los Andes, and Servicio de Anestesiología, Clínica Santa María, Santiago, Chile (D.T.); the Department of Anesthesia, General Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna (E.F.); Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, National Institute for Health Technology Assessment, and Hospital Moinhos de Vento, Porto Alegre, Brazil (C.A.P.); and the Department of Anesthesia, Hospital Paris Saint Joseph, University of Paris, Paris (P.A.).

Dr. Devereaux can be contacted at or at the David Braley Research Institute, Hamilton General Hospital, 237 Barton St. East, Hamilton, ON L8L 2X2, Canada.

A complete list of the POISE-3 Investigators is provided in the Supplementary Appendix, available at