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

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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.

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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.

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Correspondence to Sean van Diepen.

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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.

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van Diepen, S., Merrill, P.D., Carrier, M. et al. Association between CK-MB Area Under the Curve and Tranexamic Acid Utilization in Patients Undergoing Coronary Artery Bypass Surgery. J Thromb Thrombolysis 43, 446–453 (2017). https://doi.org/10.1007/s11239-017-1480-6

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