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Published on: November 11, 2012
Drug-eluting Vein Graft with Acetylsalicylic Acid-Ticagrelor-Unfractionated Heparin Complex Inhibits Early Graft
Ercan Akşit1, Tolga Kurt2, Başak Büyük3
1Department of Cardiology, Çanakkale Onsekiz Mart University School of Medicine, Çanakkale, Turkey
Insights
Local administration of acetylsalicylic acid, ticagrelor, and unfractionated heparin significantly reduced thrombus formation in bypass vein grafts. This novel approach may prevent graft loss and improve patient outcomes in coronary artery disease treatment.
Area of Science:
- Cardiovascular Surgery
- Vascular Biology
- Pharmacology
Background:
- Coronary artery bypass graft (CABG) surgery is crucial for left main and multivessel coronary artery disease.
- Early saphenous vein graft loss, up to 12% within the first month, is primarily attributed to thrombosis.
- Developing strategies to prevent early graft thrombosis is critical for improving surgical outcomes.
Purpose of the Study:
- To investigate the efficacy of locally administered anticoagulant and antiplatelet agents on early vein graft thrombosis.
- To evaluate a novel drug-eluting formulation for local application on vein grafts before bypass surgery.
Main Methods:
- Rats underwent femoral vein bypass grafting, with the vein graft tunica adventitia coated in drug-eluting pluronic F-127 gel.
- Tested drug combinations included acetylsalicylic acid, ticagrelor, and unfractionated heparin.
- Thrombus presence and area were quantified, and von Willebrand factor staining assessed graft integrity.
Main Results:
- The combination of acetylsalicylic acid, ticagrelor, and unfractionated heparin significantly reduced thrombus formation compared to control and sham groups on days 1 and 3 (p=0.001, p=0.02).
- von Willebrand factor staining was significantly lower in the triple-drug group on day 3 (p=0.005), indicating reduced endothelial damage and platelet activation.
- Local drug delivery demonstrated significant efficacy in preventing early graft thrombosis in this experimental model.
Conclusions:
- A locally administered complex of acetylsalicylic acid, ticagrelor, and unfractionated heparin effectively reduces thrombus formation in experimental vein grafts.
- This localized approach holds potential for preventing early saphenous vein graft loss post-CABG.
- Translating this local administration strategy could reduce patient morbidity and mortality associated with graft failure.
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.
