Effect of Rivaroxaban and Clopidogrel Combination Therapy on In-Stent Responses After Everolimus-Eluting Stent Implantation in a Porcine Coronary Model

Figures

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  Fig.1. Study design. (A) Schematic representation of the experimental timeline. (B) Illustration of the two subtypes of SMCs in the neointima surrounding a stent strut. (C) Representative case showing the location of the two subtypes of SMCs in a neointima stained with Masson’s trichrome. SMCs with contractile features (arrow) are close to the lumen and layered on top of the neointima whereas those with synthetic features (asterisk) are scattered within the extracellular matrix below the layer of SMCs with contractile features, close to the media. (D) Representative case of in-stent thrombus. The white arrow indicates an in-stent thrombus comprising platelet and fibrin attached to the neointimal wall. SMC, smooth muscle cell; EES, everolimus-eluting stent; OCT, optical coherence tomography

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  Fig.2. Representative cases of optical coherence tomography findings. The upper panel shows cross-sectional images of a coronary artery at 1 month after EES implantation: (A) DAPT, (B) AR, and (C) CR. The lower panel shows cross-sectional images of a coronary artery at 3 months after EES implantation: (D) DAPT, (E) AR, and (F) CR. EES, everolimus-eluting stent; DAPT, dual antiplatelet therapy (consisting of aspirin and clopidogrel administration); AR, aspirin and rivaroxaban; CR, clopidogrel and rivaroxaban

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  Fig.3. Quantitative analysis of optical coherence tomography findings. Distribution of neointimal characteristics at (A) 1 month after EES implantation and (B) 3 months after EES implantation. Comparison of mean neointimal thickness in the three groups at (C) 1 and (D) 3 months after EES implantation. Comparison of the neointimal area in the three groups at (E) 1 and (F) 3 months after EES implantation. Data are expressed as median (IQR). ＊ indicates a p -value less than 0.05; ＊＊ indicates a p -value less than 0.001. EES, everolimus-eluting stent; IQR, interquartile range; DAPT, dual antiplatelet therapy (consisting of aspirin and clopidogrel administration); AR, aspirin and rivaroxaban; CR, clopidogrel and rivaroxaban

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  Fig.4. Histological findings. (A–C) Coronary artery walls stained via HE staining and (G–I) corresponding MT-stained tissues at 1 month in the three groups (A, G: DAPT; B, H: AR; and C, I: CR). (D–F) Coronary artery walls stained via HE staining and (J–L) corresponding MT-stained tissues at 3 months in the three groups (D, J: DAPT; E, K: AR; and F, L: CR). (a–l) Magnified images corresponding to the white square in the upper panel of A–L; the white arrow in panel a indicates an in-stent thrombus. HE, hematoxylin and eosin; MT, Masson’s trichrome; DAPT, dual antiplatelet therapy (consisting of aspirin and clopidogrel administration); AR, aspirin and rivaroxaban; CR, clopidogrel and rivaroxaban

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  Fig.5. Quantitative analysis of the histological findings. (A–B) Neointimal areas in the three groups are shown at (A) 1 and (B) 3 months. (C–D) The proportion of SMCs with contractile features in the three groups, calculated using the morphometrically traced area of the layer containing SMCs with contractile features divided by the total neointimal area, is shown at (C) 1 and (D) 3 months. (E) The incidence of in-stent thrombi in 15 segments each at 1 month after everolimus-eluting stent implantation in the three groups. Data are expressed as median (IQR) or mean±SEM as appropriate. ＊ indicates a p -value less than 0.05; ＊＊ indicates a p -value less than 0.001. SMC, smooth muscle cell; IQR, interquartile range; SEM, standard error of the mean; DAPT, dual antiplatelet therapy (consisting of aspirin and clopidogrel administration); AR, aspirin and rivaroxaban; CR, clopidogrel and rivaroxaban