Comparative Evaluation of Local and Downstream Responses in Two Commercially Available Paclitaxel-Coated Balloons in Healthy Peripheral Arteries of a Swine Model.

ABSTRACT

OBJECTIVE: To investigate the local, downstream, and systemic effects of two different paclitaxel-coated balloons. DESIGN: Preclinical study in healthy peripheral arteries of a swine model, with randomized allocation of the distribution of the devices the test paclitaxel-coated balloon (PCB) (Luminor®), a control PCB (IN.PACT®), and a plain angioplasty balloon (Oceanus®), considering single (1×) and overlapping (3×) doses with simple blind histologic analysis. METHODS: Twenty animals underwent balloon angioplasty at 1× or 3× doses in the external and internal branches of both femoral arteries and were followed-up for 28 days. Post-procedural and follow-up angiography were carried out. Comprehensive necropsy and histology were used to evaluate the local, downstream and systemic effects. RESULTS: Angioplasty was successfully carried out in all animals. Significant protocol deviations appeared in three arteries (treated with Oceanus®) without clinical relevance. Those samples were excluded from the analysis. All the animals survived the follow-up period without major clinical issues. Local signs of drug toxicity were less marked with Luminor® than IN.PACT® at 1× dose, including endothelial loss (p=0.0828), intima/media inflammation (p=0.0004), transmural medial smooth muscle cell (SMC) loss (p=0.0016), wall thickness loss (p=0.0141), presence of fibrin in the vascular wall (p=0.0054), and adventitial inflammation (p=0.0080). A similar pattern was observed at the 3× dose for endothelial loss (p=0.0011), intima/media inflammation (p< 0.0001), circumferential SMC loss (p=0.0004), medial SMC replacement with proteoglycans (p=0.0014), fibrin (p=0.0034), and collagen content (p=0.0205). Downstream vascular histologic changes were mild although more prevalent in the IN.PACT® 3× group (p=0.006). No systemic effects of toxicity were detected in any of the samples analyzed. CONCLUSION: Luminor® showed better healing pattern (lower inflammation, and endothelial and muscular loss) than IN.PACT® balloon. The effect was evident at single and triple doses. The prevalence of downstream lesions, albeit low, was higher with the triple dose of IN.PACT® compared with Luminor®.