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

Balkan Med J. 2020 Aug 11;37(5):269-275. doi: 10.4274/balkanmedj.galenos.2020.2020.1.128. Epub 2020 May 1.

Abstract

Background: Bypass graft surgery remains to be an important treatment option for left main and multivessel coronary artery disease. Approximately 2% of saphenous vein grafts are lost immediately after the coronary artery bypass graft operations and 12% in the first month due to thrombosis.

Aims: To administer one anticoagulant and two antiplatelet agents in a way that locally affects the vein graft before the bypass operation and to thereby analyse their effects on early graft thrombosis.

Study design: Animal experimentation.

Methods: Since ticagrelor was used locally for the first time in this study, its efficacy in combination with other drugs (acetylsalicylic acid, acetylsalicylic acid and ticagrelor, and acetylsalicylic acid + ticagrelor + unfractionated heparin) was examined on rats including control (untreated) and sham (pluronic gel) group (n=14 for each group). Before the tunica adventitia layer of the femoral veins was bypassed to the femoral artery, it was coated with the drug-eluting pluronic F-127 gel. The presence or absence of thrombus in the vein graft samples was recorded under light microscopy. In vein graft preparations where thrombus was detected, the thrombus area (μm2) was calculated using the Axiovision software. Immunohistochemical staining was performed with the anti-rat von Willebrand factor polyclonal antibody kit.

Results: The number of preparations containing thrombus was significantly 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 and 3rd days (p=0.001 and 0.02, respectively). von Willebrand factor staining 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-ticagrelor-unfractionated heparin complex has been shown to significantly reduce thrombus formation in vein grafts in this experimental model. Local administration of these drugs, which are routinely administered orally just before stent implantations, on the vein graft before the bypass is performed can prevent the loss of vein grafts due to thrombus, thereby reducing the mortality and morbidity of these patients.

Keywords: Acetyl salicylic acid; heparin; hydrogel; thrombosis; ticagrelor; vein bypass graft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / therapeutic use
  • Aspirin / pharmacology*
  • Aspirin / therapeutic use
  • Coronary Artery Bypass / methods
  • Coronary Artery Bypass / standards*
  • Disease Models, Animal
  • Graft Enhancement, Immunologic / methods
  • Graft Enhancement, Immunologic / standards*
  • Heparin / therapeutic use
  • Pathology / methods
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Poloxamer / therapeutic use
  • Rats
  • Thrombosis / drug therapy
  • Thrombosis / prevention & control*
  • Ticagrelor / pharmacology
  • Ticagrelor / therapeutic use
  • Veins / abnormalities
  • Veins / drug effects*

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Poloxamer
  • Heparin
  • Ticagrelor
  • Aspirin