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

158 Citationer (Scopus)

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.).

Originalsprog	Engelsk
Tidsskrift	The New England journal of medicine
Vol/bind	386
Udgave nummer	21
Sider (fra-til)	1986-1997
Antal sider	12
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJMoa2201171
Status	Udgivet - 26 maj 2022

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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, bind 386, nr. 21, s. 1986-1997. https://doi.org/10.1056/NEJMoa2201171

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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 = "The 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

SN - 0028-4793

VL - 386

SP - 1986

EP - 1997

JO - The New England journal of medicine

JF - The New England journal of medicine

IS - 21

ER -

Tranexamic Acid in Patients Undergoing Noncardiac Surgery

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