Drug-eluting Vein Graft with Acetylsalicylic Acid-TicagrelorUnfractionated Heparin Complex Inhibits Early Graft Thrombosis

Drug-eluting Vein Graft with Acetylsalicylic Acid-TicagrelorUnfractionated Heparin Complex Inhibits Early Graft Thrombosis

Background: Bypass graft surgery remains to be an importanttreatment option for left main and multivessel coronary artery disease.Approximately 2% of saphenous vein grafts are lost immediately afterthe coronary artery bypass graft operations and 12% in the first monthdue to thrombosis.Aims: To administer one anticoagulant and two antiplatelet agents ina way that locally affects the vein graft before the bypass operationand to thereby analyse their effects on early graft thrombosis.Study Design: Animal experimentation.Methods: Since ticagrelor was used locally for the first time in thisstudy, its efficacy in combination with other drugs (acetylsalicylicacid, acetylsalicylic acid and ticagrelor, and acetylsalicylic acid +ticagrelor + unfractionated heparin) was examined on rats includingcontrol (untreated) and sham (pluronic gel) group (n=14 for eachgroup). Before the tunica adventitia layer of the femoral veins wasbypassed to the femoral artery, it was coated with the drug-elutingpluronic F-127 gel. The presence or absence of thrombus in the veingraft samples was recorded under light microscopy. In vein graftpreparations where thrombus was detected, the thrombus area (µm2)was calculated using the Axiovision software. Immunohistochemicalstaining was performed with the anti-rat von Willebrand factorpolyclonal antibody kit.Results: The number of preparations containing thrombus wassignificantly lower in the acetylsalicylic acid + ticagrelor +unfractionated heparin group than in the acetylsalicylic acid, control,and sham groups, according to the comparisons made on the 1st and3rd days (p=0.001 and 0.02, respectively). von Willebrand factorstaining was significantly lower in the acetylsalicylic acid + ticagrelor+ unfractionated heparin group than in the other groups on the 3rd day(p=0.005).Conclusion: Locally effective acetylsalicylic acid-ticagrelorunfractionated heparin complex has been shown to significantly reducethrombus formation in vein grafts in this experimental model. Localadministration of these drugs, which are routinely administered orallyjust before stent implantations, on the vein graft before the bypass isperformed can prevent the loss of vein grafts due to thrombus, therebyreducing the mortality and morbidity of these patients

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  • 1. Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019;40:87-165.
  • 2. Head SJ, Milojevic M, Taggart DP, Puskas JD. Current practice of stateof-the-art surgical coronary revascularization. Circulation 2017;136:1331-45.
  • 3. de Vries MR, Simons KH, Jukema JW, Braun J, Quax PH. Vein graft failure: from pathophysiology to clinical outcomes. Nat Rev Cardiol 2016;13:451-70.
  • 4. ElBardissi AW, Aranki SF, Sheng S, O’Brien SM, Greenberg CC, Gammie JS. Trends in isolated coronary artery bypass grafting: an analysis of the Society of Thoracic Surgeons adult cardiac surgery database. J Thorac Cardiovasc Surg 2012;143:273-81.
  • 5. McKavanagh P, Yanagawa B, Zawadowski G, Cheema A. Management and prevention of saphenous vein graft failure: a review. Cardiol Ther 2017;6:203-23.
  • 6. Gioffredi E, Boffito M, Calzone S, Giannitelli SM, Rainer A, Trombetta M, et al. Pluronic F127 Hydrogel Characterization and Biofabrication in Cellularized Constructs for Tissue Engineering Applications. Procedia CIRP 2016;49:125-32.
  • 7. Torsney E, Mayr U, Zou Y, Thompson WD, Hu Y, Xu Q. Thrombosis and neointima formation in vein grafts are inhibited by locally applied aspirin through endothelial protection. Circ Res 2004;94:1466-73.
  • 8. Kubisa MJ,Jezewski MP, GaseckaA, Siller-Matula JM, Postuła M.Ticagrelor--toward more efficient platelet inhibition and beyond. Ther Clin Risk Manag 2018;14:129-40.
  • 9. Preusch MR, Rusnak J, Staudacher K, Mogler C, Uhlmann L, Sievers P, et al. Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis. Drug Des Devel Ther 2016;10:2691-9.
  • 10. Andresen DM, Barker JH, Hjortdal VE. Local heparin is superior to systemic heparin in preventing arterial thrombosis. Microsurgery 2002;22:265-72.
  • 11. Zhang F, Oliva A, Kao SD, Newlin L, Buncke HJ. Microvascular vein grafts in the rat cutaneous free-flap model. J Reconstr Microsurg 1994;10:229-33.
  • 12. Bozkurt S, Arikan DC, Kurutas EB, Sayar H, Okumuş M, Çoşkun A, et al. Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: Biochemical and histopathologic evaluation. J Pediatr Surg 2012;47:1735-41.
  • 13. van Diest PJ, van Dam P, Henzen-Logmans SC, Berns E, van der Burg ME, Green J, et al. A scoring system for immunohistochemical staining: consensus report of the task force for basic research of the EORTC-GCCG. European Organization for Research and Treatment of Cancer-Gynaecological Cancer Cooperative Group. J Clin Pathol 1997;50:801-4.
  • 14. Lardenoye JH, de Vries MR, Löwik CW, Xu Q, Dhore CR, Cleutjens JP, et al. Accelerated atherosclerosis and calcification in vein grafts: a study in APOE*3 Leiden transgenic mice. Circ Res 2002;91:577-84.
  • 15. Naito M, Stirk CM, Smith EB, Thompson WD. Smooth muscle cell outgrowth stimulated by fibrin degradation products. The potential role of fibrin fragment E in restenosis and atherogenesis. Thromb Res 2000;98:165-74.
  • 16. Solo K, Lavi S, Choudhury T, Martin J, Nevis IF, Kwok CS, et al. Pre-operative use of aspirin in patients undergoing coronary artery bypass grafting: a systematic review and updated meta-analysis. J Thorac Dis 2018;10:3444-59.
  • 17. Grzesk G, Kozinski M, Navarese EP, Krzyzanowski M, Grzesk E, Kubica A, et al. Ticagrelor, but not clopidogrel and prasugrel, prevents ADP-induced vascular smooth muscle cell contraction: a placebo-controlled study in rats. Thromb Res 2012;130:65- 9.
  • 18. Hansson EC, Jideus L, Aberg B, Bjursten H, Dreifaldt M, Holmgren A, et al. Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study. Eur Heart J 2016;37:189-97.
  • 19. Lancellotti P, Musumeci L, Jacques N, Servais L, Goffin E, Pirotte B, et al. Antibacterial activity of ticagrelor in conventional antiplatelet dosages against antibiotic-resistant Gram positive bacteria. JAMA Cardiol 2019;4:596-9.
  • 20. Kilic A, Arnaoutakis DJ, Reifsnyder T, Black JH, Abularrage CJ, Perler BA, et al. Management of infected vascular grafts. Vasc Med 2016;21:53-60.
  • 21. Thompson SG, Kienast J, Pyke SD, Haverkate F, Loo De Van JC. Haemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995;332:635-41.
  • 22. Rousou LJ, Taylor KB, Lu XG, Healey N, Crittenden MD, Khuri SF, et al. Saphenous Vein Conduits Harvested by Endoscopic Technique Exhibit Structural and Functional Damage. Ann Thorac Surg 2009;87:62-70.
  • 23. Meyer DM, Rogers TE, Jessen ME, Estrera AS, Chin AK. Histologic Evidence of the Safety of Endoscopic Saphenous Vein Graft Preparation. Ann Thorac Surg 2000;70:487-91.
  • 24. Wu B, Werlin EC, Chen M, Mottola G, Chatterjee A, Lance KD, et al. Perivascular delivery of resolvinD1 inhibits neointimal hyperplasia in a rabbit vein graft model, J Vasc Surg 2018;68:188-200..
  • 25. Conte MS, Bandyk DF, Clowes AW, Moneta GL, Seely L, Lorenz TJ, et al. Results of PREVENT III: a multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery. J Vasc Surg 2006:43;742-51.
  • 26. Işıkçelik F, Ağırbaş İ, Kaya CT. An Analysis of Cost-Effectiveness of Stents Used in the Treatment of Coronary Artery Disease. Balkan Med J 2019;36:276-82.
Balkan Medical Journal-Cover
  • ISSN: 2146-3123
  • Başlangıç: 2015
  • Yayıncı: Erkan Mor
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