Investigating the dose-response of tranexamic acid for efficacy and safety in off-pump coronary artery bypass: A meta-analysis
Main Article Content
Keywords
Blood Transfusion, Dose-Response, Meta-Analysis, Off-Pump Coronary Artery Bypass, Tranexamic Acid
Abstract
Introduction: Off-pump coronary artery bypass (OPCAB) surgery carries a high risk of perioperative bleeding, often requiring blood transfusions. While tranexamic acid (TXA) is a standard antifibrinolytic agent, its ideal dosage for patients undergoing OPCAB has not been clearly established. The objective of this meta-analysis is to investigate the effectiveness, safety profile, and dose-response of TXA within this surgical context.
Methods: Following PRISMA guidelines, PubMed, ScienceDirect, and ClinicalTrials.gov were systematically searched for RCTs and observational studies comparing TXA with placebo or control. Primary efficacy measures included the volume of blood lost within 24 hours and the incidence of RBC or plasma transfusions. Safety profiles were monitored via all-cause mortality and thrombotic events, with data synthesis performed using fixed- and random-effects models and heterogeneity verified through I2 values. Pre-specified subgroup analyses by study design and administration regimen, as well as linear dose-response meta-regression, were conducted.
Results: Fourteen studies, including 5,899 patients, were analyzed. TXA significantly reduced 24-hour blood loss (MD: –193.48 mL; 95% CI: –262.86 to –124.10) and decreased RBC (RR: 0.66; 95% CI: 0.50–0.86) and plasma transfusion (RR: 0.60; 95% CI: 0.48–0.76) without increasing mortality or thromboembolic events (RR: 1.05; 95% CI: 0.69–1.59). Dose-response analysis showed no significant linear association between higher TXA doses and additional bleeding reduction (p = 0.779). Subgroup analyses indicated that the bolus-plus-continuous-infusion regimen may provide greater reductions in RBC transfusion (RR 0.57; p = 0.005) and a trend toward lower blood loss (MD –208.7 mL), whereas bolus-only showed smaller, non-significant effects.
Conclusion: TXA is safe and effective in OPCAB surgery for reducing blood loss and transfusion requirements. Escalating the dose offers no additional hemostatic benefit. A bolus-plus-continuous-infusion regimen appears more effective than bolus-only, suggesting that maintaining a sustained therapeutic concentration is more important than the total dose administered.
References
2. Koch CG, Li L, Duncan AI, Mihaljevic T, Cosgrove DM, Loop FD, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med. 2006;34(6):1608–16. Available from: https://doi.org/10.1097/01.ccm.0000217920.48559.d8
3. Wang E, Yuan X, Wang Y, Chen W, Zhou X, Hu S, et al. Blood conservation outcomes and safety of tranexamic acid in coronary artery bypass graft surgery. Int J Cardiol. 2022;348:50–6. Available from: http://doi.org/10.1016/j.ijcard.2021.12.017.
4. Wang E, Wang Y, Li Y, Hu S, Yuan S. Tranexamic acid is associated with improved hemostasis in elderly patients undergoing coronary-artery surgeries in a retrospective cohort study. Front Surg. 2023;10:1117974. Available from: http://doi.org/10.3389/fsurg.2023.1117974.
5. Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2017;376(2):136–48. Available from: http://doi.org/10.1056/nejmoa1606424.
6. Myles PS, Smith JA, Kasza J, Silbert B, Jayarajah M, Painter T, et al. Tranexamic acid in coronary artery surgery: One-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial. J Thorac Cardiovasc Surg. 2019;157(2):644-652.e9. Available from: https://doi.org/10.1016/j.jtcvs.2018.09.113.
7. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:71. Available from: https://doi.org/10.1136/bmj.n71
8. Casati V, Gerli C, Franco A, Torri G, D’Angelo A, Benussi S, et al. Tranexamic acid in off-pump coronary surgery: a preliminary, randomized, double-blind, placebo-controlled study. Ann Thorac Surg. 2001;72(2):470–5. Available from: https://doi.org/10.1016/S0003-4975(01)02802-8.
9. Casati V, Della Valle P, Benussi S, Franco A, Gerli C, Baili P, et al. Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: Comparison between on-pump and off-pump techniques. J Thorac Cardiovasc Surg. 2004;128(1):83–91. Available from: http://doi.org/10.1016/j.jtcvs.2003.10.034.
10. Khadanga P, Kanchi M, Gaur P. Effectiveness of Tranexamic Acid in Reducing Postoperative Blood Loss in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting. Cureus. 2020;12(12):e11924. Available from: http://doi.org/10.7759/cureus.11924.
11. Weingarten BR, Tran DTT, Mahaffey R, Sohmer B. Tranexamic acid for primary elective off-pump coronary artery bypass grafting surgery. Canadian journal of anaesthesia/Journal canadien d’anesthesie. 2021;68:1287–9. Available from: http://doi.org/10.1007/s12630-021-02013-2.
12. Vanek T, Jares M, Fajt R, Straka Z, Jirasek K, Kolesar M, et al. Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo). Eur J cardio-thoracic Surg. 2005;28(4):563–8. Available from: http://doi.org/10.1016/j.ejcts.2005.06.027.
13. Murphy GJ, Mango E, Lucchetti V, Battaglia F, Catapano D, Rogers CA, et al. A randomized trial of tranexamic acid in combination with cell salvage plus a meta-analysis of randomized trials evaluating tranexamic acid in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2006;132(3):475-480. Available from: http://doi.org/10.1016/j.jtcvs.2006.01.064.
14. Wei M, Jian K, Guo Z, Wang L, Jiang D, Zhang L, et al. Tranexamic acid reduces postoperative bleeding in off-pump coronary artery bypass grafting. Scand Cardiovasc J. 2006;40(2):105–9. Available from: http://doi.org/10.1080/14017430500519864.
15. Mehr-Aein A, Sadeghi M, Madani-civi M. Does tranexamic acid reduce blood loss in off-pump coronary artery bypass? Asian Cardiovasc Thorac Ann. 2007;15(4):285–9. Available from: http://doi.org/10.1177/021849230701500404.
16. Taghaddomi RJ, Mirzaee A, Attar AS, Shirdel A. Tranexamic acid reduces blood loss in off-pump coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2009;23(3):312–5. Available from: http://doi.org/10.1053/j.jvca.2008.09.018.
17. Chakravarthy M, Muniraj G, Patil S, Suryaprakash S, Mitra S, Shivalingappa B. A randomized prospective analysis of alteration of hemostatic function in patients receiving tranexamic acid and hydroxyethyl starch (130/0.4) undergoing off pump coronary artery bypass surgery. Ann Card Anaesth. 2012;15(2):105–10. Available from: http://doi.org/10.4103/0971-9784.95072.
18. Hulde N, Zittermann A, Deutsch M-A, von Dossow V, Gummert JF, Koster A. Tranexamic acid and convulsive seizures after off-pump coronary artery bypass surgery: the role of renal insufficiency. Interact Cardiovasc Thorac Surg. 2019;29(6):852–4. Available from: http://doi.org/10.1093/icvts/ivz188.
19. Ahn SW, Shim JK, Youn YN, Song JW, Yang SY, Chung SC, et al. Effect of tranexamic acid on transfusion requirement in dual antiplatelet-treated anemic patients undergoing off-pump coronary artery bypass graft surgery. Circ J. 2012;76(1):96–101. Available from: http://doi.org/10.1253/circj.cj-11-0811.
20. Wang G, Xie G, Jiang T, Wang Y, Wang W, Ji H, et al. Tranexamic acid reduces blood loss after off-pump coronary surgery: a prospective, randomized, double-blind, placebo-controlled study. Anesth Analg. 2012;115(2):239–43. Available from: http://doi.org/10.1213/ANE.0b013e3182264a11.
21. Casselman FPA, Lance MD, Ahmed A, Ascari A, Blanco-Morillo J, Bolliger D, et al. 2024 EACTS/EACTAIC Guidelines on patient blood management in adult cardiac surgery in collaboration with EBCP. J Cardiothorac Vasc Anesth. 2024;39(8):1964-2018. Available from: https://doi.org/10.1053/j.jvca.2024.10.006.