Bypass grafting: outcomes and efficiency of antiplatelet treatment

Authors: Yu.I. Grinshteyn1, A.A. Kosinova1, T.S. Mongush1 2, M.D. Goncharov1 2

Company: 1 Prof. V.F. Voyno-Yasenetskiy Krasnoyarsk State Medical University, Krasnoyarsk, 660022, Russian Federation
2 Federal Center for Cardiovascular Surgery, Krasnoyarsk, 660020, Russian Federation

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Type:  Reviews


For citation: Grinshteyn Yu.I., Kosinova A.A., Mongush T.S., Goncharov M.D. Bypass grafting: outcomes and effi- ciency of antiplatelet treatment. Creative Cardiology. 2020; 14 (2): 138–49 (in Russ.). DOI: 10.24022/1997-3187- 2020-14-2-138-149

Received / Accepted:  22.05.2020 / 29.05.2020

Keywords: bypass grafting outcomes genetic polymorphisms resistance acetylsalicylic acid clopidogrel

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The risk of developing adverse events after coronary artery bypass grafting, graft failure remains during secondary prevention with antiplatelet drugs despite successes in the development of myocardial revascularization. The caus- es of vascular events after coronary bypass surgery are multifactorial. In the pathogenesis of graft failure there are such reasons as thrombosis, conduit injury, intimal tear, reactive inflammation associated with the effect of blood pressure on the wall of the venous graft, spasm and hyperplasia. The review provides information on the outcomes of coronary bypass surgery, the reasons of graft failure by literature data. Much attention is paid to antiplatelet therapy as a secondary prevention after coronary artery bypass grafting in the light of up to date guidelines (American Thoracic Society and European Society of Cardiology), to the place of double antiplatelet therapy after intervention and its effect on outcomes. One of the important causes of graft thrombosis is primary resistance to antiplatelet drugs, due to genetic polymorphisms, therefore, one of the sections of the review is devoted to the issue of primary genetically mediated resistance to antiplatelet drugs (Acetylsalicylic acid and Clopidogrel) as a high risk factor for graft failure.


  1. Head S.J., Kieser T.M., Valk F., Huysmans H.A., Kappetein A.P. Coronary artery bypass grafting part 1 – the evoluation over first 50 years. Eur. Heart J. 2013; 34 (37): 2862–72. DOI: 10.1093/ eurheartj/eht330
  2. Mohr F.W., Morice M.C., Кappetein A.P., Eldman T.E., Stahle E., Colombo A. et al. Coronary artery bypass graft surgery vs. percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year followup of the randomised, clinical SYNTAX trial. Lancet. 2013; 381: 629–38. DOI: 10.1016/S01406736(13)60141-5
  3. Weintraub W.S., Grau-Sepulveda M.V., Weiss J.M., O’Brien S.M., Peterson E.D., Kolm P. et al. Comparative effectiveness of revascularization strategies. N. Engl. J. Med. 2012; 366: 1467–76. DOI: 10.1056/nejmc1206011
  4. Olearchyk A.S., Vasilii I.K. A pioneer of coronary revascularization by internal mammary-coronary artery grafting. J. Thorac. Cardiovasc. Surg. 1988; 96: 13–8.
  5. Magee M.J., Alexander J.H., Hafley G., Ferguson T.B., Jr., Gibson C.M., Harrington R.A. et al. Prevent IV Investigators Coronary artery bypass graft failure after on-pump and off-pump coronary artery bypass: findings from PREVENT IV. Ann. Thorac. Surg. 2008; 85: 494–500. DOI: 10.1016/j.athoracsur.2007.10.008
  6. Kulik A., Le May M.R., Voisine P., Tardif J.C., Delarochelliere R., Naidoo S. et al. Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) trial. Circulation. 2010; 122: 2680–7. DOI: 10.1161/ circulationaha.110.978007
  7. Verstraete M., Brown B.G., Chesebro J.H., Ekestroms S., Harker L.A., Henderson A.H. et al. Evaluation of antiplatelet agents in the prevention of aorto-coronary bypass occlusion. Eur. Heart J. 1986; 7: 4–13. DOI: 10.1093/oxfordjournals.eurheartj.a061955
  8. Chardigny C., Jebara V.A., Acar C., Descombes J.J., Verbeuren T.J., Carpentier A. et al. Vasoreactivity of the radial artery. Comparison with the internal mammary and gastroepiploic arteries with implications for coronary artery surgery. Circulation. 1993; 88: II115–27.
  9. Waheed A., Klosterman E., Lee J., Mishra A., Narasimha V., Tuma F. et al. Assessing the longterm patency and clinical outcomes of venous and arterial grafts used in coronary artery bypass grafting: a meta-analysis. Cureus. 2019; 11 (9): e5670. DOI: 10.7759/cureus.5670
  10. Daemen J., Boersma E., Flather M., Booth J., Stables R., Rodriguez A. et al. Long-term safety and efficacy of percutaneous coronary intervention with stenting and coronary artery bypass surgery for multivessel coronary artery disease: a meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II, and SoS trials. Circulation. 2008; 118: 1146–54. DOI: 10.1161/circulationaha.107.752147
  11. Stone G.W., Kappetein A.P., Sabik J.F., Pocock S.J., Morice M.C., Puskas J. et al. Five-year outcomes after PCI or CABG for left main coronary disease. N. Engl. J. Med. 2019; 381 (19): 1820–30. DOI: 10.1056/NEJMoa1909406
  12. Hueb W., Lopes N., Gersh B.J., Soares P.R., Ribeiro E.E., Pereira A.C. et al. Ten-year follow-up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. Circulation. 2010; 122: 949–57. DOI: 10.1161/circulationaha.109.911669
  13. Tarakji K.G., Sabik J.F., Bhudia S.K., Batizy L.H., Blackstone E.H. Temporal onset, risk factors, and outcomes associated with stroke after coronary artery bypass grafting. JAMA. 2011; 305: 381–90. DOI: 10.1001/jama.2011.37
  14. Schachner T., Zimmer A., Nagele G., Laufer G., Bonatti J. Risk factors for late stroke after coronary artery bypass grafting. J. Thorac. Cardiovasc. Surg. 2005; 130: 485–90. DOI: 10.1016/j.jtcvs. 2004.12.038
  15. Nabel E.G., Braunwald E. A tale of coronary artery disease and myocardial infarction. N. Engl. J. Med. 2012; 366: 54–63. DOI: 10.1056/nejmra1112570
  16. Mangano D.T. Aspirin and mortality from coronary bypass surgery. N. Eng. J. Med. 2002; 347: 1309–17. DOI: 10.1056/nejmoa020798
  17. Evidence Review Committee Members. Bittl J.A., Baber U., Bradley S.M., Wijeysundera D.N. Duration of dual antiplatelet therapy: a systematic review for the 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2016; 134: e156–78. DOI: 10.1161/cir.0000000000000405
  18. Neumann F.J., Sousa-Uva M., Ahlsson A., Alfonso F., Banning A.P., Benedetto U. et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur. Heart J. 2019; 40: 87–165. DOI: 10.1093/eurheartj/ehy394
  19. Wijeysundera D.N., Beattie W.S., Djaiani G., Rao V., Borger M.A., Karkouti K., Cusimanoet R.J. et al. Off-pump coronary artery surgery for reducing mortality and morbidity: metaanalysis of randomized and observational studies. J. Am. Coll. Cardiol. 2005; 46: 872–82. DOI: 10.1016/ j.jacc.2005.05.064
  20. Shumkov K.V., Lefterova N.P., Pak N.L., Kakuchaya T.T., Smirnova Yu.Yu., Polunina V.M. et al. Coronary artery bypass grafting under conditions of cardiopulmonary bypass and on a working heart: a comparative analysis of the immediate and long-term results and postoperative complications (cardiac arrhythmias, cognitive and neurological disorders, rheological features and the state of the hemostatic system). Creative Cardiology. 2009; 1: 28–50 (in Russ.).
  21. Wang Y., Chen S., Shi J.-W., Dong N.-G. Benefit and safety of dual antiplatelet therapy after coronary artery bypass grafting for offpump CABG: a systematic review and meta-analysis. Br. J. Med. Medical. Res. 2015; 9 (11): 1–15. DOI: 10.9734/bjmmr/2015/19433
  22. Deo S.V., Dunlay S.M., Shah I.K., Altarabsheh S.E., Erwin P.J., Boilson B.A. et al. Dual antiplatelet therapy after coronary artery bypass grafting: Is there any benefit? A systematic review and meta-analysis. J. Card. Surg. 2013; 28 (2): 109–16. DOI: 10.1111/jocs.12074
  23. Mannacio V.A., Di T.L., Antignan A., Amicis V.D., Vosa C. Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypaSS occlusion After off-pump procedures) randomised study. Heart. 2012; 98: 1710–5. DOI: 10.1136/heartjnl2012-302449
  24. Sun J.C., Teoh K.H., Lamy A., Sheth T., Ellins M.L., Jung H. et al. Randomized trial of aspirin and clopidogrel versus aspirin alone for the prevention of coronary artery bypass graft occlusion: the preoperative aspirin and postoperative antiplatelets in coronary artery bypass grafting study. Am. Heart J. 2010; 160: 1178–84. DOI: 10.1016/j.ahj.2010.07.035
  25. Gao G., Zheng Z., Pi Y., Lu B., Lu J., Hu S. Aspirin plus clopidogrel therapy increases early venous graft patency after coronary artery bypass surgery a single-center, randomized, controlled trial. J. Am. Coll. Cardiol. 2010; 56: 1639–43. DOI: 10.1016/j.jacc.2010.03.104
  26. Nocerino A.G., Achenbach S., Taylor A.J. Meta analysis of effect of single versus dual antiplatelet therapy on early patency of bypass conduits after coronary artery bypass grafting. Am. J. Cardiol. 2013; 112: 1576–9. DOI: 10.1016/j.amjcard.2013.07.017
  27. Leon N., Jackevicius C.A. Use of aspirin and clopidogrel after coronary artery bypass graft surgery. Ann. Pharmacother. 2012; 46: 678–87. DOI: 10.1345/aph.1q692
  28. Гринштейн Ю.И., Савченко А.А., Филоненко И.В., Савченко Е.А. Зилт в сравнении с ацетилсалициловой кислотой у пациентов с атеросклерозом коронарных артерий после аортокоронарного шунтирования. Основные результаты исследования ЗЕВС: эффективность препаратов, механизм резистентности к ацетилсалициловой кислоте, ближайшие и отдаленные клинические результаты. Кардиоваскулярная терапия и профилактика. 2009; 8 (8): 36–43. [Grinshtein Yu.I., Savchenko A.A., Filonenko I.V., Savchenko E.A. Zyllt and acetylsalicylic acid in coronary atherosclerosis patients after coronary artery bypass graft intervention/ Main results of the ZEUS Study: medication effectiveness, acetylsalicylic acid resistance mechanisms, short and long-term clinical outcomes. Cardiovascular Therapy and Prevention. 2009; 8 (8): 36–43 (in Russ.).]
  29. Wiviott S.D., Braunwald E., McCabe C.H., Montalescot G., Ruzyllo W., Gottlieb S. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. 2007; 357: 2001–15. DOI: 10.1056/nejmoa0706482
  30. Varenhorst C., Alstrom U., Scirica B.M., Hogue C.W., Asenblad N., Storey R.F. et al. Factors contributing to the lower mortality with ticagrelor compared with clopidogrel in patients undergoing coronary artery bypass surgery. J. Am. Coll. Cardiol. 2012; 60: 1623–30. DOI: 10.1016/j.jacc. 2012.07.021
  31. Zhao Q., Zhu Y., Xu Zh., Cheng Z., Mei J., Chen X. et al. Effect of ticagrelor plus aspirin, ticagrelor alone, or aspirin alone on saphenous vein graft patency 1 year after coronary artery bypass grafting. a randomized clinical trial. JAMA. 2018; 319 (16): 1677–86. DOI: 10.1001/jama.2018.3197
  32. Wu H., Wang J., Sun H., Wang X., Hu X., Ma W. et al. Preoperative continuation of aspirin therapy may improve perioperative saphenous venous graft patency after off-pump coronary artery bypass grafting. Ann. Thorac. Surg. 2015; 99 (2): 576–80. DOI: 10.1016/j.athoracsur.2014.07.074
  33. Wang G., Bainbridge D., Martin J., Cheng D. The efficacy of an intraoperative cell saver during cardiac surgery: a meta-analysis of randomized trials. Anesth. Analg. 2009; 109: 320–30. DOI: 10.1213/ ane.0b013e3181aa084c
  34. Grinshtein Yu.I., Kosinova A.A., Grinshtein I.Yu., Kovalev A.V., Sukhovolsky V.G., Savchenko A.A. Clinical and laboratory features of patients with ischemic heart disease resistant to acetylsalicylic acid in the perioperative period of coronary artery bypass surgery: results of an open prospective study. Rational Pharmacotherapy in Cardiology. 2016; 12 (3): 265–71 (in Russ.).
  35. Golukhova E.Z., Ryabinina M.N., Bulaeva N.I., Grigoryan M.V., Kubova M.Ch. Platelet reactivity on the background of dual antiplatelet therapy after coronary artery stenting: genetic polymorphisms and clinical variants. Creative Cardiology. 2013; 2: 15–27 (in Russ.).
  36. Rebrova T.Yu., Muslimova E.F., Afanasyev S.A., Sergienko T.N., Repin A.N. Clopidogrel resistance and P2RY12 and GPIIIA gene polymorphisms in patients with chronic ischemic heart disease. Clinical Medicine. 2013; 91 (8): 29–31 (in Russ.).]/li>
  37. Halushka M.K., Halushka P.V. Why are some individuals resistant to the cardioprotective effects of aspirin? Could it be thromboxaneA 2? Circulation. 2002; 105: 1620–2. DOI: 10.1161/ 01.cir.0000015422.86569.52
  38. Li Q., Chen B.L., Ozdemir V., Ji W., Mao Y.M., Wang L.C. et al. Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Pharmacogenomics. 2007; 86: 577–86. DOI: 10.2217/14622416.8.6.577
  39. Liu H., Xu Z, Sun C., Gu D., Teng X., Zhao Y. et al. A variant in COX-2 gene is associated with left main coronary artery disease and clinical outcomes of coronary artery bypass grafting. Biomed. Res. Int. 2017; 2017: 1–6. DOI: 10.1155/2017/2924731
  40. Jefferson B.K., Foster J.H., McCarthy J.J., Ginsburg G., Parker A., Kottke-Marchant K. et al. Aspirin resistance and a single gene. Am. J. Cardiol. 2005; 95: 805–8. DOI: 10.1016/j.amjcard.2004.11.045
  41. Cooke G.E., Bray P.F., Hamlington J.D., Pham D.M., Goldschmidt-Clermont P.J. PLA2 polymorphism and efficacy of aspirin. Lancet. 1998; 351: 1253. DOI: 10.1016/s0140-6736(05)79320-x
  42. Wang Z., Gao F., Men J., Yang J., Modi P., Wei M. Polymorphisms and high on-aspirin platelet reactivity after off-pump coronary artery bypass grafting. Scand. Cardiovasc. J. 2013; 47 (4): 194–9. DOI: 10.3109/14017431.2013.800640
  43. Wang Z., Gao F., Men J., Ren J., Modi P., Wei M. Aspirin resistance in off-pump coronary artery bypass grafting. Eur. J. Cardiothorac. Surg. 2012; 41 (1): 108–12. DOI: 10.1016/j.ejcts.2011.04.021
  44. Grove E.L., Hvas A.M., Mortensen S.B., Larsen S.B., Kristensen S.D. Effect of platelet turnover on whole blood platelet aggregation in patients with coronary artery disease. J. Thromb. Haemost. 2011; 9: 185–91. DOI: 10.1111/j.15387836.2010.04115.x
  45. Grinshtein Y.I., Kosinova A.A., Grinshtein I.Y., Subbotina T.N., Savchenko A.A. The prognostic value of combinations of genetic polymorphisms in the ITGB3, ITGA2, and CYP2C19*2 genes in predicting cardiovascular outcomes after coronary bypass grafting. Test. Mol. Biomarkers. 2018; 22 (4): 259–65. DOI: 10.1089/gtmb.2017.0177
  46. Emiroglu O., Durdu S., Egin Y., Akar A.R., Alakoc Y.D., Zaim C. et al Thrombotic gene polymorphisms and postoperative outcome after coronary artery bypass graft surgery. J. Cardiothorac. Surg. 2011; 6: 120. DOI: 10.1186/1749-8090-6-120
  47. Muehlschlegel J.D., Liu K.-Y., Perry T.E., Fox A.A., Collard C.D., Shernan S.K. et al. Body and CABG genomics investigators. chromosome 9p21 variant predicts mortality after coronary artery bypass graft surgery. Circulation. 2010; 122: S60–5. DOI: 10.1161/circulationaha.109.924233
  48. Pai C.C., Lin Y.W., Tsai Y.T., Loh S.H., Lin C.Y., Lin C.S. et al. A thrombomodulin gene polymorphism (C1418T) is associated with early outcomes in patients undergoing coronary artery bypass graft surgery with a conventional cardiopulmonary bypass during hospitalization. Medicines (Basel). 2017; 23; 4 (2): E22. DOI: 10.3390/ medicines4020022
  49. Stępień E., Krawczyk S., Kapelak B., Sobczyński R., Stoliński J., Wypasek E. et al. Effect of the E-selectin gene polymorphism (S149R) on platelet activation and adverse events after coronary artery surgery. Arch. Med. Res. 2011; 42 (5): 375–81. DOI: 10.1016/j.arcmed.2011.07.007
  50. Wysocka A., Cybulski M., Berbeć H., Wysokiński A., Stążka J., Zapolski T. Prognostic value of paraoxonase 1 in patients undergoing coronary artery bypass grafting surgery. Med. Sci. Monit. 2014; 20: 594–600. DOI: 10.12659/MSM.890025
  51. Kosinova A.A., Mongush T.S., Goncharov M.D., Subbotina T.N., Semashchenko K.S., Kochmareva G.Yu., Grinshtein Yu.I. A study of the association of V64OL polymorphism (rs6133) in the Pselectin gene with acetylsalicylic acid resistance in patients with coronary heart disease after coronary artery bypass grafting. Rational Pharmacotherapy in Cardiology. 2019; 15 (3): 343–8 (in Russ.)
  52. Shah A.A., Haynes C., Craig D.M., Sebek J., Grass E., Abramson K. et al. Genetic variants associated with vein graft stenosis after coronary artery bypass grafting. Heart Surg. Forum. 2015; 18 (1): E1–5. DOI: 10.1532/hsf.1214
  53. Simon T., Verstuyft C., Mary-Krause M., Quteineh L., Drouet E., Méneveau N. et al. Genetic determinants of response to clopidogrel and cardiovascular events. N. Engl. J. Med. 2009; 360 (4): 363–75. DOI: 10.1056/nejmoa0808227
  54. Wallentin L., James S., Storey R.F., Armstrong M., Barratt B.J., Horrow J. et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet. 2010; 376: 1320–8. DOI: 10.1016/s0140-6736(10)61274-3
  55. Marchini J.F.M., Pinto M.R., Novaes G.C., Badran A.V., Pava~o R.B., Figueiredo G.L. et al. Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients. Braz. J. Med. Biol. Res. 2017; 50 (1): e5660. DOI: 10.1590/1414-431x20165660
  56. Bonello L., Pansieri M., Mancini J., Bonello R., Maillard L., Barnay P. et al. High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes. J. Am. Coll. Cardiol. 2011; 58 (5): 467–73. DOI: 10.1016/j.jacc.2011.04.017
  57. Teng R. Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral antiplatelet agent ticagrelor. Clini. Pharmacokin. 2012; 51 (5): 305–18. DOI: 10.1097/MCA.0b013e328360

About Authors

Yuriy I. Grinshteyn, Dr. Med. Sc., Professor, Chief of Chair,
Aleksandra A. Kosinova, Cand. Med. Sc., Assistant Professor,
Taira S. Mongush, Applicant, Cardiologist
Maksim D. Goncharov, Applicant, Laboratory Diagnostics Physician

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, Director of Bakoulev National Medical Research Center for Cardiovascular Surgery