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 Short; Maria 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; Ossian Gundel; Viktor Moseholm; Diana B. Jensen; Mia K Hansen; Grethe Bendixen; Anne Sofie Jensen; Sanne Dahl Thorsager Olesen; Naomi Nadler; Mette Krogh Østerby; Mojgan Vazin Kjeldsen; Jawad Ahmad Zahid; Nessn Azawi; Ismail Gögenur; Eske Kvanner Aasvang; Niels Brandt Højlund-Hansen; Theis Simon  Bak; Thomas Kistorp; Martin Andreas Røder

doi:10.1056/NEJMoa2201171

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)

Abstract

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 ClinicalTrials.gov number, NCT03505723.).

Original language	English
Journal	The New England journal of medicine
Volume	386
Issue number	21
Pages (from-to)	1986-1997
Number of pages	12
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa2201171
Publication status	Published - 26 May 2022

Keywords

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

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10.1056/NEJMoa2201171

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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., ... Røder, M. A. (2022). Tranexamic Acid in Patients Undergoing Noncardiac Surgery. The New England journal of medicine, 386(21), 1986-1997. https://doi.org/10.1056/NEJMoa2201171

Devereaux, PJ, Marcucci, M, Painter, TW, Conen, D, Lomivorotov, V, Sessler, DI, Chan, MTV, Borges, FK, Martínez-Zapata, MJ, Wang, C-Y, Xavier, D, Ofori, SN, Wang, MK, Efremov, S, Landoni, G, Kleinlugtenbelt, YV, Szczeklik, W, Schmartz, D, Garg, AX, Short, TG, Wittmann, M, Meyhoff, CS, Amir, M, Torres, D, Patel, A, Duceppe, E, Ruetzler, K, Parlow, JL, Tandon, V, Fleischmann, E, Polanczyk, CA, Lamy, A, Astrakov, SV, Rao, M, Wu, WKK, Bhatt, K, de Nadal, M, Likhvantsev, VV, Paniagua, P, Aguado, HJ, Whitlock, RP, McGillion, MH, Prystajecky, M, Vincent, J, Eikelboom, J, Copland, I, Balasubramanian, K, Turan, A, Bangdiwala, SI, Stillo, D, POISE-3 Investigators, Søgaard, M , Gundel, O , Moseholm, V , Jensen, DB , Hansen, MK , Bendixen, G , Jensen, AS, Olesen, SDT, Nadler, N, Østerby, MK, Kjeldsen, MV, Zahid, JA, Azawi, N, Gögenur, I, Aasvang, EK, Højlund-Hansen, NB, Bak, TS , Kistorp, T & Røder, MA 2022, 'Tranexamic Acid in Patients Undergoing Noncardiac Surgery', The New England journal of medicine, vol. 386, no. 21, pp. 1986-1997. https://doi.org/10.1056/NEJMoa2201171

@article{8ce976e670394ccabe379af3a1a0a90d,

title = "Tranexamic Acid in Patients Undergoing Noncardiac Surgery",

abstract = "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 ClinicalTrials.gov number, NCT03505723.).",

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

author = "Devereaux, {P J} and Maura Marcucci and Painter, {Thomas W} and David Conen and Vladimir Lomivorotov and Sessler, {Daniel I} and Chan, {Matthew T V} and Borges, {Flavia K} and Mart{\'i}nez-Zapata, {Mar{\'i}a J} and Chew-Yin Wang and Denis Xavier and Ofori, {Sandra N} and Wang, {Michael K} and Sergey Efremov and Giovanni Landoni and Kleinlugtenbelt, {Ydo V} and Wojciech Szczeklik and Denis Schmartz and Garg, {Amit X} and Short, {Timothy G} and Maria Wittmann and Meyhoff, {Christian S} and Mohammed Amir and David Torres and Ameen Patel and Emmanuelle Duceppe and Kurt Ruetzler and Parlow, {Joel L} and Vikas Tandon and Edith Fleischmann and Polanczyk, {Carisi A} and Andre Lamy and Astrakov, {Sergey V} and Mangala Rao and Wu, {William K K} and Keyur Bhatt and {de Nadal}, Miriam and Likhvantsev, {Valery V} and Pilar Paniagua and Aguado, {Hector J} and Whitlock, {Richard P} and McGillion, {Michael H} and Michael Prystajecky and Jessica Vincent and John Eikelboom and Ingrid Copland and Kumar Balasubramanian and Alparslan Turan and Bangdiwala, {Shrikant I} and David Stillo and {POISE-3 Investigators} and Marlene S{\o}gaard and Ossian Gundel and Viktor Moseholm and Jensen, {Diana B.} and Hansen, {Mia K} and Grethe Bendixen and Jensen, {Anne Sofie} and Olesen, {Sanne Dahl Thorsager} and Naomi Nadler and {\O}sterby, {Mette Krogh} and Kjeldsen, {Mojgan Vazin} and Zahid, {Jawad Ahmad} and Nessn Azawi and Ismail G{\"o}genur and Aasvang, {Eske Kvanner} and H{\o}jlund-Hansen, {Niels Brandt} and Bak, {Theis Simon} and Thomas Kistorp and R{\o}der, {Martin Andreas}",

note = "Copyright {\textcopyright} 2022 Massachusetts Medical Society.",

year = "2022",

month = may,

day = "26",

doi = "10.1056/NEJMoa2201171",

language = "English",

volume = "386",

pages = "1986--1997",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "21",

}

TY - JOUR

T1 - Tranexamic Acid in Patients Undergoing Noncardiac Surgery

AU - Devereaux, P J

AU - Marcucci, Maura

AU - Painter, Thomas W

AU - Conen, David

AU - Lomivorotov, Vladimir

AU - Sessler, Daniel I

AU - Chan, Matthew T V

AU - Borges, Flavia K

AU - Martínez-Zapata, María J

AU - Wang, Chew-Yin

AU - Xavier, Denis

AU - Ofori, Sandra N

AU - Wang, Michael K

AU - Efremov, Sergey

AU - Landoni, Giovanni

AU - Kleinlugtenbelt, Ydo V

AU - Szczeklik, Wojciech

AU - Schmartz, Denis

AU - Garg, Amit X

AU - Short, Timothy G

AU - Wittmann, Maria

AU - Meyhoff, Christian S

AU - Amir, Mohammed

AU - Torres, David

AU - Patel, Ameen

AU - Duceppe, Emmanuelle

AU - Ruetzler, Kurt

AU - Parlow, Joel L

AU - Tandon, Vikas

AU - Fleischmann, Edith

AU - Polanczyk, Carisi A

AU - Lamy, Andre

AU - Astrakov, Sergey V

AU - Rao, Mangala

AU - Wu, William K K

AU - Bhatt, Keyur

AU - de Nadal, Miriam

AU - Likhvantsev, Valery V

AU - Paniagua, Pilar

AU - Aguado, Hector J

AU - Whitlock, Richard P

AU - McGillion, Michael H

AU - Prystajecky, Michael

AU - Vincent, Jessica

AU - Eikelboom, John

AU - Copland, Ingrid

AU - Balasubramanian, Kumar

AU - Turan, Alparslan

AU - Bangdiwala, Shrikant I

AU - Stillo, David

AU - POISE-3 Investigators

A2 - Søgaard, Marlene

A2 - Gundel, Ossian

A2 - Moseholm, Viktor

A2 - Jensen, Diana B.

A2 - Hansen, Mia K

A2 - Bendixen, Grethe

A2 - Jensen, Anne Sofie

A2 - Olesen, Sanne Dahl Thorsager

A2 - Nadler, Naomi

A2 - Østerby, Mette Krogh

A2 - Kjeldsen, Mojgan Vazin

A2 - Zahid, Jawad Ahmad

A2 - Azawi, Nessn

A2 - Gögenur, Ismail

A2 - Aasvang, Eske Kvanner

A2 - Højlund-Hansen, Niels Brandt

A2 - Bak, Theis Simon

A2 - Kistorp, Thomas

A2 - Røder, Martin Andreas

PY - 2022/5/26

Y1 - 2022/5/26

N2 - 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 ClinicalTrials.gov number, NCT03505723.).

AB - 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 ClinicalTrials.gov number, NCT03505723.).

KW - Antifibrinolytic Agents/adverse effects

KW - Canada

KW - Hemorrhage/etiology

KW - Humans

KW - Surgical Procedures, Operative

KW - Thrombosis/chemically induced

KW - Tranexamic Acid/adverse effects

UR - http://www.scopus.com/inward/record.url?scp=85128013076&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa2201171

DO - 10.1056/NEJMoa2201171

M3 - Journal article

C2 - 35363452

VL - 386

SP - 1986

EP - 1997

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 21

ER -

Tranexamic Acid in Patients Undergoing Noncardiac Surgery

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Keywords

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