Biologic Drug Effect and Particulate Embolization of Drug-Eluting Stents versus Drug-Coated Balloons in Healthy Swine Femoropopliteal Arteries

Summary 

It has become clear that addition of antineoplastic drugs to intervention in peripheral vascular disease lesions has improved patency on all intervention platforms vs no drug. However, Drug coated Balloon (DCB) vs Drug eluting stent (DES) in femoro-popliteal artery remains an area of controversy with limited to non-existent robust direct head to head comparison studies.

Researchers recently published an animal study that contributes significant insight into this ongoing controversy. In their preclinical study in normal pig vessels they compared the biologic effects of POBA + DES vs DES + DCB vs DCB + BMS vs DCB alone in a direct head to head fashion. After 1 month, they measured local vessel histomorphometric parameters and objectively evaluated histologic changes in the downstream vessels for potential harmful effects of distal embolic paclitaxel. Angiographic diameter measurements were also performed.

The DES group demonstrated the best biological effect regardless of preceding POBA or DCB vs DCB + BMS or DCB alone. Of further significant note is that, downstream histological changes of damage from distal paclitaxel embolization were only seen in the limbs were a DCB had been utilized. No significant difference in luminal loss in all groups at 1 month.



Figure 1. Representative histologic images of the biologic responses to DCB + DES, PTA + DES, DCB + BMS, and DCB alone in swine iliofemoral arteries. Fibrin deposition in each treatment group is demonstrated in the middle panels, whereas depth of SMC loss is demonstrated with yellow arrows in the lower panels. Mild medial SMC loss with focal proteoglycan accumulation is observed in the DCB-alone group (a–c). Moderate medial SMC loss is observed in the DCB + BMS group, with minimal fibrin around stent struts (d–f). The greatest biologic drug effect is observed in the DCB + DES (g–i) and PTA + DES (j–l) groups in the form of extensive medial SMC loss and extensive fibrin around stent struts

Commentary

This animal study provides useful scientific concepts to assist in improving our understanding in addressing the current clinical conundrum of DCB vs stenting in lesions that otherwise have no mechanical issues causing flow limitations post intervention. The study findings suggest DES has superior biologic effects regardless of preceding PTA with POBA or DCB. Subgroup analysis of the study also suggests there is non-uniform biologic effects with DCB vs with DES.

We also learn from this study that DCBs appear to be the only ones associated with histologically significant downstream vessel damage/changes from paclitaxel distal embolization. Overall, the findings in principle appear to favor DES in terms of biological efficacy and potential histological side effects. It is also interesting to note in the same study that at 1 month there were no statistically significant differences in luminal change at angiography between all the groups studied. Although this is clearly a very short term follow up it raises the question about how significant these histological advantages may translate to meaningful clinical benefits or disadvantages in real world clinical patient scenarios.

With all these points in mind, the pragmatic appeal of treating a patient without having to leave a metal foreign body will require a lot more robust data and trials to move the dial in favor of DES in uncomplicated vascular lesions.

The study has several limitations, most of which are well acknowledged by the authors. I would add that the biological benefits of DES with regards to Smooth muscle Cell (SMC) loss may have been confounded and potentially overestimated by the natural SMC loss that occurs with stent centrifugal compression. Despite these limitations, the study moves the ball forward in helping our understanding of this controversial topic and perhaps sets up a good platform for robust true direct head to head clinical RCTs.

Click here for abstract

Torii S, Yahagi K, Mori H, et al. Biologic Drug Effect and Particulate Embolization of Drug-Eluting Stents versus Drug-Coated Balloons in Healthy Swine Femoropopliteal Arteries. J Vasc Interv Radiol. 2018; 29:1041-1049.

Post Author:
Rodrick C Zvavanjanja, MD, MSc, FRCR, DABR(VIR/DR)
Assistant Professor
Department of Diagnostic and Interventional Radiology
University of Texas at Houston McGovern Medical School
@RodZvavanjanja