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®.