Introduction: Drug-coated balloons (DCBs) have emerged as an effective treatment for patients with symptomatic peripheral arterial disease in the femoropopliteal arteries. They have been shown to be superior to balloon angioplasty (PTA) in large, multicenter randomized trials. After the introduction of the first DCB, the Bard Peripheral Vascular Lutonix .035˝ over-the-wire DCB, there have been several entrants into the DCB market. However, multiple clinical and preclinical studies have illustrated there are differences in performance and safety between the different products. The various DCB technologies differ in their design of excipient coatings and the drug form (crystallinity) of the combinations. These design features can produce differences in effective drug delivery to target tissue while avoiding non-target effect (ie, minimize emboli). In a previously published study, the Lutonix .035˝ and the Medtronic In.Pact Admiral were tested and compared for downstream embolic events. The In.Pact DCB illustrated increased downstream embolic debris and higher paclitaxel levels. The findings of embolic debris from DCB coatings are of potential importance and may be further compounded in patients with claudication and more complex critical limb ischemia (CLI) with limited flow reserve. Information regarding embolic debris may be important in the selection of DCBs for patient care.
Objectives: Different excipient/drug formulations unique to individual DCBs may influence embolic safety characteristics in distal non-target peripheral vascular territories through embolization of released particulates. A comparator study of three DCBs in commercial use – the In.Pact Admiral, Boston Scientific Ranger, and Spectranetics Stellarex – in healthy swine was therefore performed to assess which balloon produced more downstream emboli and tissue reaction.
Methods: Three-times overlapping 80 mm DCBs for each device were assessed in 24 femoral arteries of 12 swine with 28-day follow-up for downstream embolic events and debris. In.Pact Admiral was used as a control, as its downstream emboli and effect have been previously studied and published. Histologic analysis of arterial wall and skeletal muscle and coronary band downstream from the external or internal femoral arteries was performed. This analysis was supported by an analytic measurement of paclitaxel levels. The gastrocnemius, gluteal, and gracilis are skeletal muscle territories distal to the external femoral artery and the coronary corium (ie, coronary band) is a highly vascularized structure that gives rise to the outer layers of the hoof wall and resembles the nail bed of a human finger.
Results: For all DCBs tested, regions of increased proteoglycan were accompanied by the loss of medial smooth muscle cells mainly extending nearly one-third to complete transmural involvement with restricted circumferential extension. Medial fibrin was present for all cohorts. The percentage of sections with downstream vascular changes in arterioles were greatest for In.Pact > Stellarex > Ranger (43%, 36%, and 25%, respectively). Embolic crystalline material was seen for all cohorts and followed a similar trend. Drug analysis in parallel tissues illustrated the highest paclitaxel concentrations in non-target coronary band tissues for Stellarex > In.Pact > Ranger (962.3 ng/g, 911.3 ng/g, and 822.5 ng/g, respectively).
Conclusion: All DCBs tested exhibited downstream effects of paclitaxel drug and/or downstream emboli. The In.Pact control exhibited similar behavior as published from a previous study on downstream emboli. The new DCBs tested, Stellarex and Ranger, exhibited downstream vascular changes and the Stellarex DCB exhibited the highest downstream coronary band paclitaxel concentration at 28 days. The potential downstream embolic effects with certain DCB use may present a concern that may influence the selection of available catheter technologies.