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 2 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. Postprocedural 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 3 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 = .0828), intima/media inflammation (P = .0004), transmural medial smooth muscle cell (SMC) loss (P = .0016), wall thickness loss (P = .0141), presence of fibrin in the vascular wall (P = .0054), and adventitial inflammation (P = .0080). A similar pattern was observed at the 3× dose for endothelial loss (P = .0011), intima/media inflammation (P < .0001), circumferential SMC loss (P = .0004), medial SMC replacement with proteoglycans (P = .0014), fibrin (P = .0034), and collagen content (P = .0205). Downstream vascular histologic changes were mild although more prevalent in the IN.PACT® 3× group (P = .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®.

Keywords: Drug-coated balloon; Local effect, downstream embolization; Percutaneous transluminal angioplasty; Peripheral artery disease; Preclinical study.