Advertisement

Journal of Thrombosis and Thrombolysis

, Volume 43, Issue 4, pp 446–453 | Cite as

Association between CK-MB Area Under the Curve and Tranexamic Acid Utilization in Patients Undergoing Coronary Artery Bypass Surgery

  • Sean van DiepenEmail author
  • Peter D. Merrill
  • Michel Carrier
  • Jean-Claude Tardif
  • Mihai Podgoreanu
  • John H. Alexander
  • Renato D. Lopes
Article

Abstract

Myonecrosis after coronary artery bypass graft (CABG) surgery is associated with excess mortality. Tranexamic acid (TA), an anti-fibrinolytic agent, has been shown to reduce peri-operative blood loss without increasing the risk of myocardial infarction (MI); however, no large study has examined the association between TA treatment and post-CABG myonecrosis. In the MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II trial, inverse probability weighting of the propensity to receive TA was used to test for differences among the 656 patients receiving and 770 patients not receiving TA. The primary outcome was creatine kinase MB (CK-MB) area under the curve (AUC) through 24 h. The secondary outcome was 30-day cardiovascular death or MI. Patients who received TA were more frequently female, had a previous MI, heart failure, low molecular weight heparin therapy, on-pump CABG, valvular surgery, and saphenous vein or radial grafts. The median 24-h CK-MB AUC was higher in TA-treated patients [301.9 (IQR 196.7–495.6) vs 253.5 (153.4–432.5) ng h/mL, p < 0.001]. No differences in the 30-day incidence of cardiovascular death or MI were observed (8.7 vs 8.3%, adjusted OR 0.99; 95% CI 0.67–1.45, p = 0.948). In patients undergoing CABG, TA use was associated with a higher risk of myonecrosis; however, no differences were observed in death or MI. Future larger studies should be directed at examining the pathophysiology of TA myonecrosis, and its association with subsequent clinical outcomes.

Keywords

Myonecrosis Tranexamic acid CABG CK-MB 

Notes

Acknowledgements

We would like to thank Karen Pieper for her statistical assistance and Peter Hoffmann for copyediting the manuscript.

Authors’ contributions

S.V.D. conception and design, analysis, interpretation of data, drafting the article, final approval of the version to be published, and agreement to be accountable for all aspects of the work thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; P.D.M.: conception and design, analysis and interpretation of data, drafting the article, final approval of the version to be published, and agreement to be accountable for all aspects of the work thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; M.C., J.C.T., M.P., J.H.A.: conception and design, acquisition of data, interpretation of data, revisions for critically for important intellectual content, final approval of the version to be published, and agreement to be accountable for all aspects of the work thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; R.D.L.: conception and design, analysis and interpretation of data, revisions for critically for important intellectual content, final approval of the version to be published, and agreement to be accountable for all aspects of the work thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding

This analysis was funded by the Duke Clinical Research Institute. The sponsor of the randomized trial from which this work was derived had no role in this study.

Compliance with ethical standards

Conflict of interest

J.C.T. has received research support from Amarin, AstraZeneca, DalCor, Eli-Lilly, Hoffmann-LaRoche, Merck, Pfizer, Sanofi and Servier, and honoraria (to his institution) from Hoffmann-LaRoche, Pfizer, Servier and Valeant. Disclosures for J.H.A. and R.D.L. are available at https://www.dcri.org/about-us/conflict-of-interest. The remaining authors have disclosed that they do not have any conflicts of interest.

Supplementary material

11239_2017_1480_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 18 KB)

References

  1. 1.
    Murphy GJ, Reeves BC, Rogers CA, Rizvi SIA, Culliford L, Angelini GD (2007) Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 116:2544–2552CrossRefPubMedGoogle Scholar
  2. 2.
    Reeves BC, Murphy GJ (2008) Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery. Curr Opin Cardiol 23:607–612CrossRefPubMedGoogle Scholar
  3. 3.
    Dunn CJ, Goa KL (1999) Tranexamic acid: a review of its use in surgery and other indications. Drugs 57:1005–1032CrossRefPubMedGoogle Scholar
  4. 4.
    Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER, Shore-Lesserson LJ, Goodnough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J, Baker RA, Dickinson TA, FitzGerald DJ, Likosky DS, Shann KG (2011) 2011 Update to the society of thoracic surgeons and the society of cardiovascular anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 91:944–982CrossRefPubMedGoogle Scholar
  5. 5.
    Karski JM, Teasdale SJ, Norman P, Carroll J, VanKessel K, Wong P, Glynn MFX (1995) Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid: double-blind, randomized clinical trial. J Thorac Cardiovasc Surg 110:835–842CrossRefPubMedGoogle Scholar
  6. 6.
    Armellin G, Casella S, Guzzinati S, Pasini L, Marcassa A, Giron G (2001) Tranexamic acid in aortic valve replacement. J Cardiothorac Vasc Anesth 15:331–335CrossRefPubMedGoogle Scholar
  7. 7.
    Casati V, Bellotti F, Gerli C, Franco A, Oppizzi M, Cossolini M, Calori G, Benussi S, Alfieri O, Torri G (2001) Tranexamic acid administration after cardiac surgery. Anesthesiology 94:8–14CrossRefPubMedGoogle Scholar
  8. 8.
    Brown JR, Birkmeyer NJO, O’Connor GT (2007) Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation 115:2801–2813CrossRefPubMedGoogle Scholar
  9. 9.
    Henry D, Carless P, Fergusson D, Laupacis A (2009) The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. CMAJ 180:183–193CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Later AFL, Maas JJ, Engbers FHM, Versteegh MIM, Bruggemans EF, Dion RAE, Klautz RJM (2009) Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery. Eur J Cardiothorac Surg 36:322–329CrossRefPubMedGoogle Scholar
  11. 11.
    Fergusson DA, Hébert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, Teoh K, Duke PC, Arellano R, Blajchman MA, Bussières JS, Côté D, Karski J, Martineau R, Robblee JA, Rodger M, Wells G, Clinch J, Pretorius R (2008) A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 358:2319–2331CrossRefPubMedGoogle Scholar
  12. 12.
    Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, McGuinness S, Byrne K, Chan MT, Landoni G, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network (2016) Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med. doi: 10.1056/NEJMoa1606424 Google Scholar
  13. 13.
    Costa MA, Carere RG, Lichtenstein SV, Foley DP, de Valk V, Lindenboom W, Roose PCH, van Geldorp TR, Macaya C, Castanon JL, Fernandez-Avilèz F, Gonzáles JH, Heyer G, Unger F, Serruys PW (2001) Incidence, predictors, and significance of abnormal cardiac enzyme rise in patients treated with bypass surgery in the Arterial Revascularization Therapies Study (ARTS). Circulation 104:2689–2693CrossRefPubMedGoogle Scholar
  14. 14.
    Klatte K, Chaitman BR, Theroux P, Gavard JA, Stocke K, Boyce S, Bartels C, Keller B, Jessel A (2001) Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release: results from the GUARDIAN trial. J Am Coll Cardiol 38:1070–1077CrossRefPubMedGoogle Scholar
  15. 15.
    Croal BL, Hillis GS, Gibson PH, Fazal MT, El-Shafei H, Gibson G, Jeffrey RR, Buchan KG, West D, Cuthbertson BH (2006) Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery. Circulation 114:1468–1475CrossRefPubMedGoogle Scholar
  16. 16.
    Domanski MJ, Mahaffey K, Hasselblad V, Brener SJ, Smith PK, Hillis G, Engoren M, Alexander JH, Levy JH, Chaitman BR, Broderick S, Mack MJ, Pieper KS, Farkouh ME (2011) Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery. JAMA 305:585–591CrossRefPubMedGoogle Scholar
  17. 17.
    Mehta RH, Alexander JH, Emery R, Ellis SJ, Hasselblad V, Khalil A, Carrier M, Harrington RA, Tardif J-C (2008) A randomized, double-blind, placebo-controlled, multicenter study to evaluate the cardioprotective effects of MC-1 in patients undergoing high-risk coronary artery bypass graft surgery: MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery Trial (MEND-CABG) II—study design and rationale. Am Heart J 155:600–608CrossRefPubMedGoogle Scholar
  18. 18.
    Alexander JH, Emery RW Jr, Carrier M, Ellis SJ, Mehta RH, Hasselblad V, Menasche P, Khalil A, Cote R, Bennett-Guerrero E, Mack MJ, Schuler G, Harrington RA, Tardif J-C (2008) Efficacy and safety of pyridoxal 5′-phosphate (MC-1) in high-risk patients undergoing coronary artery bypass graft surgery: the MEND-CABG II randomized clinical trial. JAMA 299:1777–1787CrossRefPubMedGoogle Scholar
  19. 19.
    Adler MSC, Brindle W, Burton G, Gallacher S, Hong FC, Manelius I, Smith A, Ho W, Alston RP, Bhattacharya K (2011) Tranexamic acid is associated with less blood transfusion in off-pump coronary artery bypass graft surgery: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth 25:26–35CrossRefGoogle Scholar
  20. 20.
    Dryden P, O’Connor JP, Jamieson WRE, Reid I, Ansley D, Sadeghi H, Burr L, Munro AI, Merrick P (1997) Tranexamic acid reduces blood loss and transfusion in reoperative cardiac surgery. Can J Anaesth 44:934–941CrossRefPubMedGoogle Scholar
  21. 21.
    Karski J, Djaiani G, Carroll J, Iwanochko M, Seneviratne P, Liu P, Kucharczyk W, Fedorko L, David T, Cheng D (2005) Tranexamic acid and early saphenous vein graft patency in conventional coronary artery bypass graft surgery: a prospective randomized controlled clinical trial. J Thorac Cardiovascular Surg 130:309–314CrossRefGoogle Scholar
  22. 22.
    Mangano DT, Tudor IC, Dietzel C (2006) The risk associated with aprotinin in cardiac surgery. N Engl J Med 354:353–365CrossRefPubMedGoogle Scholar
  23. 23.
    Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD (2012) Third universal definition of myocardial infarction. Circulation 126:2020–2035CrossRefPubMedGoogle Scholar
  24. 24.
    Royston D (1995) Blood-sparing drugs: aprotinin, tranexamic acid, and epsilon-aminocaproic acid. Int Anesthesiol Clin 33(1):155–179CrossRefPubMedGoogle Scholar
  25. 25.
    Odabaş AR, Çetinkaya R, Selçuk Y, Kaya H, Coşkun Ü (2001) Tranexamic-acid-induced acute renal cortical necrosis in a patient with haemophilia A. Nephrol Dial Transplant 16:189–190CrossRefPubMedGoogle Scholar
  26. 26.
    Koo JR, Lee YK, Kim YS, Cho WY, Kim HK, Won NH (1999) Acute renal cortical necrosis caused by an antifibrinolytic drug (tranexamic acid). Nephrol Dial Transplant 14:750–752CrossRefPubMedGoogle Scholar
  27. 27.
    Myles PS, Smith J, Knight J, Cooper DJ, Silbert B, McNeil J, Esmore DS, Buxton B, Krum H, Forbes A, Tonkin A (2008) Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial: rationale and design. Am Heart J 155:224–230CrossRefPubMedGoogle Scholar
  28. 28.
    Diprose P, Herbertson MJ, O’Shaughnessy D, Deakin CD, Gill RS (2005) Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage. Br J Anaesth 94:271–278CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Sean van Diepen
    • 1
    Email author
  • Peter D. Merrill
    • 2
  • Michel Carrier
    • 3
  • Jean-Claude Tardif
    • 3
  • Mihai Podgoreanu
    • 2
    • 4
  • John H. Alexander
    • 2
  • Renato D. Lopes
    • 2
  1. 1.Department of Critical Care and Division of Cardiology, 2C2 Cardiology Walter MacKenzie CenterUniversity of Alberta HospitalEdmontonCanada
  2. 2.Duke Clinical Research InstituteDuke University School of MedicineDurhamUSA
  3. 3.Montreal Heart InstituteUniversité de MontréalMontrealCanada
  4. 4.Divisions of Cardiothoracic Anesthesia and Critical Care MedicineDuke University School of MedicineDurhamUSA

Personalised recommendations