IN.PACT™ Admiral™ DCB: Safety and Effectiveness in Treating Complex Lesions
Discussing trends demonstrated in existing clinical data and practice for the endovascular treatment of complex femoropopliteal lesions.
In relation to femoropopliteal lesions, the term complex inspires in each of us our own personal definition, usually comprising morphologic elements of the target lesion such as length, degree of calcium, and presence of an occlusion. Our approach is equally personal, as it is often based on the physician’s training, experience, opinion leader presentations, and interpretation of available clinical data. As a result, I am pleased to be accompanied in this supplement by clinicians representing various specialties, each with their own experiences and philosophies, to offer their perspectives on treating complex femoropopliteal lesions.
CURRENT CLINICAL DATA FOR COMPLEX LESIONS
At some point, I expect most physicians will have all seen a graphic similar to Figure 1. I always warn that comparing patency rates across multiple trials is fraught with limitations due to various types of bias as well as variations in populations, lesions, study protocols, definitions, and follow-up, among others. However, Figure 1 does offer us insight into the overall clinical data landscape of core laboratory–adjudicated femoropopliteal studies of FDA class 3 devices and their respective control arms when employed. Since the modest beginning of Figure 1’s data points more than 10 years ago, the landscape has certainly evolved, but a few particular trends have become apparent and seem to persist. This article highlights and discusses each of these trends.
DATA EXIST MOSTLY FOR LESIONS ≤ 10 CM
At first glance, we see a majority of data clustered toward shorter lesions. As you might expect, these lesions range from approximately 5 to 12 cm and typically comprise the simple disease process often encountered in investigational device exemption (IDE) studies that device manufacturers are required to perform to gain FDA approval (Figure 1; data points 1-8, 10-16, 23-33, 36-38). However, these lesions are fairly uncommon in many of our own practices, and extrapolating these data sets to longer, more complex lesion types beyond the IDE studies is challenging. Surveying the data for more moderate lesion lengths of approximately 15 to 20 cm, we are limited to five studies consisting of the prespecified in-stent restenosis (ISR) cohort of IN.PACT Global (Figure 1; 17); the randomized ISR cohorts treated with either heparin-bound stent graft or percutaneous transluminal angioplasty (PTA) of the RELINE study (Figure 1; 9, 40); the cohorts of heparin-bound stent graft and nonbound stent graft randomized against their bare-metal stent (BMS) control arms of VIASTAR (Figure 1; 34, 42) and VIBRANT (Figure 1; 35, 41), respectively; and the ZEPHYR single-arm Japan postmarket approval study of a drug-eluting stent (DES) (Figure 1; 39). Beyond 20 cm, the data are similarly sparse, with outcomes reported from four drug-coated balloon (DCB) studies and a single peripheral stent graft study (Figure 1; 18-21, 43). The message here is that although many of us practice in the domain beyond 15 cm, the vast majority of adjudicated outcomes lie below this range.
CONVENTIONAL PTA PATENCY CLUSTErs TOWARD LOW END
Once we dig into the landscape, we see the points representing PTA clustering toward the low patency end of the shorter lesions. Although certainly a variation exists within the PTA cohorts, we have to keep in mind that the study protocols, endpoint definitions, and technical practices evolved during the course of these studies. For instance, compare the two control arms of the Zilver PTX and RESILIENT randomized trials, which posted PTA patency rates of 32.8% and 36.7%, respectively (Figure 1; 1, 3), in lesions of approximately 6.5 cm, against a contemporary DCB control arm such as the ILLUMENATE Pivotal trial control patency rate of 70.9% (Figure 1; 7). In doing so, we see how factors such as randomization after successful predilatation and sustained balloon inflation complicate comparisons across studies. Despite this variability, PTA clearly occupies the low end of the patency spectrum.
PRIMARY PATENCY IS INVERSELY PROPORTIONAL TO LESION LENGTH
The next trend we see is the declining patency rate associated with increasing lesion length, underscoring a pitfall of extrapolating data captured in short-lesion studies to our own practices, where much longer lesions are commonplace. Less is known about length-dependent performance of DESs given the lack of available data. The core lab–adjudicated ZEPHYR DES study reports positive 12-month outcomes in a challenging population exhibiting a mean lesion length of 17 cm (Figure 1; 39), which adds to the experience of shorter-lesion DES cohorts studied as part of the Zilver PTX and IMPERIAL trials (Figure 1; 36-38). Diverging from independently adjudicated patency outcomes, both the all-comers Japan Zilver PTX postmarket surveillance study and a single-center retrospective analysis demonstrate patency consistent with outcomes observed in the shorter-lesion randomized controlled trial (RCT) despite reported mean lesion lengths of 14.7 and 24.2 cm, respectively.29,30 Importantly, further analysis of Phillips et al did discern higher patency in DES-treated lesions ≤ 20 cm compared with those > 20 cm, which also exhibited a higher proportion of occlusions. This once again suggests a length-dependency effect on patency for lesions treated with DESs.30 However, as stent length increases, the discussion of stent fracture cannot be totally ignored. Consider 12-month outcomes of two cohorts employing the same stent: the RESILIENT study’s BMS arm reported a fracture rate of 3.1% for lesions averaging 7.1 cm (Figure 1; 24) compared with a fracture rate of 27.1% for lesions averaging 11.8 cm in the TIGRIS study BMS arm (Figure 1; 33). Despite being a well-known phenomenon,31 the consequences of lesion length and fracture are not fully understood or consistent between stent designs.
IN.PACT GLOBAL PRESPECIFIED IMAGING COHORTS BUCK THE TREND IN LESION LENGTH
Very few adjudicated data exist for treatment of lesion lengths > 20 cm; the only data available is composed of four DCB cohorts (Figure 1; 18-21) and a single heparin-bound stent graft study (Figure 1; 43). Historically, studies in this range came late in the evolution of these data. Zeller et al reported the outcomes associated with the 25-cm heparin-bound stent graft in lesions averaging 26.5 cm, (Figure 1; 43) with interestingly non–length-dependent patency rates similar to those reported in the RELINE and VIASTAR studies (Figure 1; 40,42). For the DCB cohorts, the Lutonix Long Lesion study reported a mean lesion length of 21.3 cm (Figure 1; 18), the chronic total occlusion and long lesion prespecified imaging cohorts of the IN.PACT Global study posted mean lesion lengths of 22.8 and 26.4 cm, respectively (Figure 1; 19, 20), and the SFA-Long Study performed by Micari et al averaged 25.2-cm lesion lengths (Figure 1; 20). Importantly, when considering the IN.PACT™ Admiral™ DCB (Medtronic) cohorts, the patency definition is identical across the two RCTs and the three prespecified imaging cohorts of IN.PACT Global, therefore facilitating patency comparisons across cohorts and underscoring the consistency in patency beyond 20-cm lesions, despite variation in study populations and lesion morphologies. However, it is also worth highlighting that these long-lesion DCB studies are not without significant stent usage; in three of these four cohorts, provisional stent rates of approximately 40% and higher are reported (Figure 1; 18, 19, 21). The one exception to this trend of provisional stenting is reported by the SFA-Long study that demonstrated similar patency results while only resorting to stenting in 10.5% of their lesions (Figure 1; 20). In this supplement, we have commentary from Prof. Micari on his approach to PTA vessel preparation and minimizing stent use when employing DCB in challenging lesions.
SUPPORT FOR EXPANDING INDICATION
Finally, to support recent FDA indication expansion of the IN.PACT Admiral DCB to lesion lengths up to 36 cm, a post hoc analysis was performed on all core lab–adjudicated IN.PACT Global subjects exhibiting lesions ≥ 18 cm, including ISR subjects (Figure 1; 22). The outcomes are consistent with the other IN.PACT Admiral DCB trends as demonstrated in Figure 1, and 96 (42.5%) of 227 patients received provisional stenting of various lengths. This observation indicates that a DCB with optimal use of stents led to patency similar to the simpler lesions treated with DCBs alone.
From the simple, single-digit lesion lengths to the truly long lesions, we certainly have more insight today than 10 years ago. Each of us is left with our own interpretation of these data, but a few trends are evident: (1) PTA is at the low end of the performance range; (2) length-dependent patency is a consistent observation for PTA and BMSs; and (3) DCBs and, if needed, provisional stent optimization may yield consistent patency with apparently less lesion length dependence. Of course, the data continue to evolve, and we hope it will not take us another 10 years to identify new trends, possibly aided by the evolution of lesion preparation with new specialty balloon technologies, atherectomy, and yet-to-be-developed devices that may be used prior to DCBs. For now, we will leave Figure 1 behind, and begin our panel discussion to explore individual opinions on complex lesion treatment.
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30. Phillips JA, Falls A, Kolluri R, et al. Full drug-eluting stent jacket: two-year results of a single-center experience with Zilver PTX stenting for long lesions in the femoropopliteal arteries. 2018;25:295-301.
31. Scheinert D, Scheinert S, Sax J, et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol. 2005;4:312-315.
Gary M. Ansel, MD, FACC
System Medical Chief, Vascular Services
Associate Medical Director
OhioHealth Research Institute
Assistant Clinical Professor of Medicine
Department of Medicine
University of Toledo Medical Center
Disclosures: Consulting or advisory board for Medtronic, Boston Scientific Corporation, Abbott Vascular, Surmodics, Philips, CR Bard, and Cook Medical.