Peri-interventional triple therapy with dabigatran improves vasomotion and promotes endothelialization in porcine coronary stenting model

$\textbf {Objective:}$ We evaluated the short and long-term effect of peri-interventional dabigatran therapy on vasomotion, endothelialization, and neointimal formation in a porcine coronary artery stenting model. $\textbf {Background:}$ Stenting of coronary arteries induces local inflammation, impairs vasomotion and delays endothelialization. $\textbf {Methods:}$ Twenty-eight animals underwent percutaneous coronary intervention (PCI) with drug eluting stents. Sixteen pigs started dabigatran therapy 4 days prior to PCI and continued for 4 days post-stenting, while 12 animals served as controls. Post-stenting dual antiplatelet therapy (75 mg clopidogrel and 100 mg aspirin) was continued in both groups until termination. Immediately post-stenting and at day 3 optical coherence tomography (OCT) was performed in all animals, followed by euthanasia of 8 dabigatran and 4 control animals. The remaining pigs (8 of each group) were followed up for 1 month, with control angiography and OCT. Tissue burden (degree of peri-strut structure—thrombus and/or fibrin) was evaluated. After euthanasia coronary arteries were harvested for $\textit {in-vitro}$ myometry and histology. $\textbf {Results:}$ Thrombin generation was lower ($\it p$ < 0.001) and tissue burden (0.83 $\pm$ 0.98 vs. 3.0 $\pm$ 2.45; $\it p$ = 0.031) was significantly decreased in dabigatran treated animals. After 3 days post-PCI endothelium-dependent vasodilation was significantly improved (77 $\pm$ 40% vs. 41 $\pm$ 31%, $\it p$ = 0.02) in dabigatran animals. Neither quantitative angiography nor histomorphometry showed differences between the groups. Endothelialization was faster in the dabigatran group as compared with controls ($\it p$ = 0.045). Conclusion: Short-term peri-interventional triple therapy with dabigatran, aspirin, and clopidogrel led to an enhanced endothelium dependent vasodilation and faster endothelialization. However, neointimal formation 1-month after stent implantation was comparable between groups