“Cilostazol as a Non-inferiority pharmacologic option to Paclitaxel in Early Intimal Hyperplasia inhibition after venous balloon angioplasty in a Rabbit model. A preliminary Study”

Abstract The development of venous intimal hyperplasia (VIH) has not been fully studied. At present, there are not drugs approved for VIH inhibition; in order to investigate such alternatives, we aimed to compare Paclitaxel with Cilostazol in VIH early inhibition in a preliminary experimental model of balloon angioplasty. Twenty-eight male New Zealand rabbits were randomly divided into two groups: Cilostazol (A) and Paclitaxel (B) and underwent femoral vein barotrauma by a 4 mm balloon angioplasty. VIH model was previously tested in controls obtaining 80% increase of subintimal area (SIA) compared to veins without injury (from 0.12 mm2 [SD 0.05] to 0.86 mm2 [SD 0.08]). Group A received 20 mg/kg twice daily, group B angioplasty was performed with Paclitaxel coated balloon as single dose. Seven days later rabbits were euthanized, vein tissue samples were taken for histological analysis. Primary endpoint was SIA measure expressed in mm2, delta off difference was 0.21 mm2. Other measurements were immunohistochemistry expression of hypoxia inducible factor (HIF) -1alpha, platelet derived growth factor (PDGF) and smooth muscle actin (SMA), as surrogates of cell migration and oxidative stress. SIA of group A was 0.33 mm2 (0.15, 95% CI 0.24 to 0.42 mm2), for group B of 0.31 mm2 (SD 0.14, 95% CI 0.22 to 0.40 mm2). Both drugs showed reduction of 61% and 63% respectively in SIA, compared with controls. The difference between both drugs was 0.0193 mm2 (95% CI -0.1175 to 0.156 mm2), statistical difference was founded in HIF-1alpha expression between both groups.