Tranexamic acid in patients undergoing coronary-artery surgery

Paul S. Myles, Julian A. Smith, Andrew Forbes, Brendan Silbert, the ATACAS Investigators of the ANZCA Clinical Trials Network

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. METHODS In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P = 0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P = 0.001), and seizures occurred in 0.7% and 0.1%, respectively (P = 0.002 by Fisher's exact test). CONCLUSIONS Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).

Original languageEnglish
Pages (from-to)136-148
Number of pages13
JournalNew England Journal of Medicine
Volume376
Issue number2
DOIs
Publication statusPublished - 12 Jan 2017

Cite this

Myles, Paul S. ; Smith, Julian A. ; Forbes, Andrew ; Silbert, Brendan ; the ATACAS Investigators of the ANZCA Clinical Trials Network. / Tranexamic acid in patients undergoing coronary-artery surgery. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 2. pp. 136-148.
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title = "Tranexamic acid in patients undergoing coronary-artery surgery",
abstract = "BACKGROUND Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. METHODS In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7{\%}) in the tranexamic acid group and in 420 patients (18.1{\%}) in the placebo group (relative risk, 0.92; 95{\%} confidence interval, 0.81 to 1.05; P = 0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4{\%} of the patients in the tranexamic acid group and in 2.8{\%} of the patients in the placebo group (P = 0.001), and seizures occurred in 0.7{\%} and 0.1{\%}, respectively (P = 0.002 by Fisher's exact test). CONCLUSIONS Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).",
author = "Myles, {Paul S.} and Smith, {Julian A.} and Andrew Forbes and Brendan Silbert and Mohandas Jayarajah and Thomas Painter and Cooper, {D. James} and Silvana Marasco and John McNeill and Bussieres, {Jean S.} and Shay McGuinness and Kelly Byrne and Chan, {Matthew T. V.} and Giovanni Landoni and Sophie Wallace and {the ATACAS Investigators of the ANZCA Clinical Trials Network}",
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Myles, PS, Smith, JA, Forbes, A, Silbert, B & the ATACAS Investigators of the ANZCA Clinical Trials Network 2017, 'Tranexamic acid in patients undergoing coronary-artery surgery' New England Journal of Medicine, vol. 376, no. 2, pp. 136-148. https://doi.org/10.1056/NEJMoa1606424

Tranexamic acid in patients undergoing coronary-artery surgery. / Myles, Paul S.; Smith, Julian A.; Forbes, Andrew; Silbert, Brendan; the ATACAS Investigators of the ANZCA Clinical Trials Network.

In: New England Journal of Medicine, Vol. 376, No. 2, 12.01.2017, p. 136-148.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Tranexamic acid in patients undergoing coronary-artery surgery

AU - Myles, Paul S.

AU - Smith, Julian A.

AU - Forbes, Andrew

AU - Silbert, Brendan

AU - Jayarajah, Mohandas

AU - Painter, Thomas

AU - Cooper, D. James

AU - Marasco, Silvana

AU - McNeill, John

AU - Bussieres, Jean S.

AU - McGuinness, Shay

AU - Byrne, Kelly

AU - Chan, Matthew T. V.

AU - Landoni, Giovanni

AU - Wallace, Sophie

AU - the ATACAS Investigators of the ANZCA Clinical Trials Network

PY - 2017/1/12

Y1 - 2017/1/12

N2 - BACKGROUND Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. METHODS In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P = 0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P = 0.001), and seizures occurred in 0.7% and 0.1%, respectively (P = 0.002 by Fisher's exact test). CONCLUSIONS Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).

AB - BACKGROUND Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. METHODS In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P = 0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P = 0.001), and seizures occurred in 0.7% and 0.1%, respectively (P = 0.002 by Fisher's exact test). CONCLUSIONS Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).

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JO - New England Journal of Medicine

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Myles PS, Smith JA, Forbes A, Silbert B, the ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic acid in patients undergoing coronary-artery surgery. New England Journal of Medicine. 2017 Jan 12;376(2):136-148. https://doi.org/10.1056/NEJMoa1606424