Author + information
- Received April 3, 2014
- Revision received May 24, 2014
- Accepted June 24, 2014
- Published online October 14, 2014.
- Thomas Zeller, MD∗,
- Iris Baumgartner, MD†,
- Dierk Scheinert, MD‡,
- Marianne Brodmann, MD§,
- Marc Bosiers, MD‖,
- Antonio Micari, MD, PhD¶,
- Patrick Peeters, MD, PhD#,
- Frank Vermassen, MD, PhD∗∗,
- Mario Landini, MS††,
- David B. Snead, PhD††,
- K. Craig Kent, MD‡‡,
- Krishna J. Rocha-Singh, MD§§∗ (, )
- IN.PACT DEEP Trial Investigators
- ∗Department of Angiology, Universitäts Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany
- †Swiss Cardiovascular Center, Division of Angiology, University Hospital, Inselspital, Bern, Switzerland
- ‡Center of Vascular Medicine, Park Hospital Leipzig, Leipzig, Germany
- §Department of Angiology, Medical University Graz, Graz, Austria
- ‖Department of Vascular Surgery, A.Z. Sint-Blasius, Dendermonde, Belgium
- ¶Invasive Cardioangiology GVM Care and Research, Palermo, Italy
- #Department of Cardiovascular & Thoracic Surgery, Imelda Hospital, Bonheiden, Belgium
- ∗∗Department of Vascular Surgery, Ghent University Hospital, Ghent, Belgium
- ††Medtronic Endovascular Therapies, Santa Rosa, California
- ‡‡Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
- §§Prairie Heart Institute at St. John’s Hospital, Springfield, Illinois
- ↵∗Reprint requests and correspondence:
Dr. Krishna J. Rocha-Singh, Prairie Heart Institute at St. John’s Hospital, 619 East Mason Street, Springfield, Illinois 62191.
Background Drug-eluting balloons (DEB) may reduce infrapopliteal restenosis and reintervention rates versus percutaneous transluminal angioplasty (PTA) and improve wound healing/limb preservation.
Objectives The goal of this clinical trial was to assess the efficacy and safety of IN.PACT Amphirion drug-eluting balloons (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with critical limb ischemia (CLI).
Methods Within a prospective, multicenter, randomized, controlled trial with independent clinical event adjudication and angiographic and wound core laboratories 358 CLI patients were randomized 2:1 to IA-DEB or PTA. The 2 coprimary efficacy endpoints through 12 months were clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). The primary safety endpoint through 6 months was a composite of all-cause mortality, major amputation, and CD-TLR.
Results Clinical characteristics were similar between the 2 groups. Significant baseline differences between the IA-DEB and PTA arms included mean lesion length (10.2 cm vs. 12.9 cm; p = 0.002), impaired inflow (40.7% vs. 28.8%; p = 0.035), and previous target limb revascularization (32.2% vs. 21.8%; p = 0.047). Primary efficacy results of IA-DEB versus PTA were CD-TLR of 9.2% versus 13.1% (p = 0.291) and LLL of 0.61 ± 0.78 mm versus 0.62 ± 0.78 mm (p = 0.950). Primary safety endpoints were 17.7% versus 15.8% (p = 0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the IA-DEB arm versus the PTA arm (8.8% vs. 3.6%; p = 0.080).
Conclusions In patients with CLI, IA-DEB had comparable efficacy to PTA. While primary safety was met, there was a trend towards an increased major amputation rate through 12 months compared to PTA. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733)
Balloon angioplasty (percutaneous transluminal angioplasty [PTA]) of infrapopliteal arteries in critical limb ischemia (CLI) is a common, established practice worldwide. The development of long, low-profile balloons has contributed to their widespread adoption in the treatment of this complex disease process, which is characterized by multilevel, multivessel, long-segment atherosclerosis (1–6). However, despite suboptimal long-term patency rates and poor correlation between primary patency and limb preservation (7), PTA is an accepted “first-line” therapy to re-establish direct blood flow to the foot in patients with suitable anatomy where procedural success is favorably balanced by relatively minimal risk. With low procedure-related complication rates, infrapopliteal PTA frequency has increased and, when combined with an adequate wound care program, is associated with acceptable near-term limb preservation rates reported in small single-center experiences and registries in CLI patient cohorts. However, reintervention to re-establish limb perfusion after clinical restenosis is associated with increased morbidity and mortality rates in this sick patient population (8,9) and poorer surgical outcomes when repeated revascularization procedures ultimately fail (10,11). Durable infrapopliteal vessel patency may promote faster, more sustained, complete wound healing (12) and limb preservation, and is a desired revascularization goal.
Paclitaxel drug-eluting balloons (DEBs) have recently been introduced to reduce vessel restenosis and, potentially, to facilitate sustained wound healing and improve limb preservation. Two single-center, self-adjudicated studies, the first retrospective (13) and the second randomized (14), suggested that use of the paclitaxel-eluting IN.PACT Amphirion DEB (IA-DEB) may reduce infrapopliteal vessel restenosis and reintervention rates. Therefore, we sought to confirm these preliminary findings in this first large, multicenter, randomized, controlled trial of IA-DEB and PTA in CLI patients.
The IN.PACT DEEP (RandomIzed AmPhirion DEEP DEB vs StAndard PTA for the treatment of below the knee CriTical limb ischemia) trial (15) rationale and design, statistical hypothesis/methodology primary and secondary endpoints, and inclusion and exclusion criteria were previously published (16). The IN.PACT DEEP trial is a prospective, multicenter, patient-blinded randomized controlled trial of IA-DEB (Medtronic, Santa Rosa, California) versus PTA for the treatment of infrapopliteal arterial disease in patients presenting with CLI.
The study hypothesis of superior efficacy of IA-DEB versus PTA (primary efficacy endpoint) was on the basis of 2 coprimary endpoints assessed through 12 months: clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). CD-TLR was evaluated in the entire patient population, while LLL was evaluated in a subcohort of patients meeting specific eligibility criteria (including lesion length ≤10 cm) and consented for 12-month angiographic follow-up. The primary safety endpoint is a composite of all-cause death, major amputation, and CD-TLR revascularization rate assessed through 6 months and is on the basis of a noninferiority hypothesis with a 10% margin.
CD-TLR is defined as any TLR associated with deterioration of Rutherford category and/or increasing size of pre-existing wounds and/or occurrence of new wounds as adjudicated by the wound core laboratory.
Device success is defined as exact device deployment according to the instructions for use as documented in at least 2 different imaging projections. Technical success is defined as successful vascular access and completion of the endovascular procedure and immediate morphological success with endovascular procedure with ≤50% residual diameter reduction of the treated lesion on completion angiography. Procedural success is defined as the combination of technical success, device success, and absence of procedural complications. Procedural complications included abrupt closure, distal embolization, perforation, aneurysm, vasospasm, thrombus, and recoil as adjudicated by the Angiographic Core Lab (SynvaCor, Springfield, Illinois). Patient follow-up through 5 years is ongoing; the primary safety and efficacy endpoints were reached at 6 and 12 months, respectively. All patients with iliac or femoropopliteal inflow lesions were treated accordingly in the setting of the index procedure. Failure to obtain <30% residual stenosis post-treatment constituted an exclusion criterion.
The trial was independently adjudicated, supervised, and monitored, and included angiographic, and wound core laboratories (16). A clinical event committee, data safety monitoring board, and external data monitoring with 100% source data verification were also included in the trial protocol. An electronic reader (SilhouetteMobile, Aranz Medical Limited, Auckland, New Zealand), consisting of a laser-assisted camera, was used to obtain accurate, operator-independent wound areas and depths at baseline and at follow-up; all data and images were analyzed by the Wound Core Lab (SynvaCor, Springfield, Illinois). Both wound and angiographic core laboratories were blinded to the assigned treatment. The IN.PACT DEEP trial was conducted in compliance with the principles of the Declaration of Helsinki, ISO 14155, and Good Clinical Practices guidelines. Written informed consent was obtained from all enrolled patients and ethics committees of all investigational sites approved the trial protocol. Statistical methods and analysis were performed by the study sponsor and were previously reported in detail (16). All patients with iliac or femoropopliteal inflow lesions were treated accordingly during the index procedure. Failure to obtain <30% residual stenosis post-treatment constituted an exclusion criterion.
The total sample size for the IN.PACT DEEP trial was calculated at 357 subjects, which fully powers the coprimary endpoints of LLL (80%) for superiority and the primary composite safety endpoint (80%) on the basis of initial estimates of event rates and effect sizes of the 2 arms for noninferiority, IA-DEB and PTA randomized 2:1. The primary coefficacy endpoint of 12-month TLR was powered to 65% with the indicated sample size.
The first primary efficacy endpoint was LLL, assessed at 12 months or at the time of TLR. The second primary efficacy endpoint was incidence of CD-TLR assessed through 12 months. Each was tested for superiority in comparison of the randomized groups. All analyses were on the basis of the intention-to-treat principle. Statistical analyses were performed using IBM SPSS Software. An interim analysis was performed on the first 150 subjects, incurring a 0.2% adjustment to the alpha level.
Primary efficacy endpoint: angiographic cohort
The statistical hypothesis of superiority for LLL at 12 months was assessed using a 2-sample Student t test of IA-DEB versus PTA, with a 4.8% 2-sided alpha.
Primary efficacy endpoint: clinical cohort
For the efficacy endpoint of 12-month TLR, the statistical hypothesis was tested using Fisher’s exact test for proportions of IA-DEB versus PTA with 4.8% 2-sided alpha.
Primary safety endpoint
The primary safety endpoint for the trial was a composite of all-cause death, major amputation, and CD-TLR at 6 months tested for noninferiority with a 10% margin and 4.8% 1-sided alpha.
From September 2009 to July 2012, a total of 358 patients were enrolled across 13 European sites (Online Appendix) and randomized 2:1 to IA-DEB versus PTA with all subjects evaluated in the clinical cohort and 167 of these subjects studied in the angiographic cohort. Patient distribution within the 2 cohorts and through 12 months is described in the patient flow diagram (Figure 1).
Key clinical characteristics
Patients in the IA-DEB and PTA arms presented predominantly with Rutherford Category 5 (84.1% and 77.3%, respectively) when compared with Rutherford Category 4 (14.2% and 17.6%, respectively) and 6 (1.7% and 4.2%, respectively). The salient demographic features of the 2 cohorts are detailed in Table 1 and reflect the challenging nature of CLI patients: 75.7% and 68.9% were diabetics, 8.6% and 12.5% had renal insufficiency (glomerular filtration rate <30 ml/min), and 6.7% and 3.4% were confined to bed in the IA-DEB and PTA arms, respectively. None of the previously mentioned characteristics differ significantly between the 2 arms. Prior TLR was significantly higher in the IA-DEB (32.2%) versus the PTA (21.8%) arm (p = 0.047).
Key angiographic characteristics
Impaired inflow was significantly higher in the IA-DEB arm (40.7%) versus the PTA (28.8%) arm (p = 0.035). Target lesions were significantly longer (12.9 ± 9.5 cm vs. 10.2 ± 9.1 cm) in the PTA arm versus the IA-DEB arm (p = 0.002). Total occlusions were 38.6% in the IA-DEB arm and 45.9% in the PTA arm (p = 0.114). An incomplete pedal loop occurred frequently, with at least 1 portion of the posterior-plantar, the plantar arch, or the anterior dorsalis path being either occluded or stenotic in 78.2% of IA-DEB arm patients and 70.6% of PTA arm patients (p = 0.118). Conversely, a complete pedal loop was rarely present in IA-DEB (5.4%) and PTA patients (7.6%; p = 0.485), while complete pedal loop occlusion was present in 7.1% of IA-DEB patients and 11.8% of PTA patients (p = 0.163). Mean lesion lengths in the 167-patient angiography cohort were 5.91 ± 4.17 cm and 7.97 ± 7.46 cm (p = 0.060) with total occlusion present in 31.6% and 32.7% (p = 1.000) of the IA-DEB versus PTA treatment arms, respectively. The percentages of patients evaluable for angiographic core laboratory analysis were 52.6% and 52.7% in the IA-DEB and PTA arms, respectively.
Key wound characteristics
Ischemic wound size and distribution of the treated limbs are described in Table 2. Wound location in the IA-DEB and PTA arms included the foot in 79.3% and 79.1% (p = 0.818); toe wounds occurred in 64.9% and 63.1% (p = 0.799) and heel wounds in 8.0% and 15.5% (p = 0.072), respectively. By core laboratory evaluation, the wound area was 4.8 ± 11.0 cm2 and 6.9 ± 14.5 cm2 (p = 0.296) and wound depth was 0.8 ± 1.3 mm and 1.8 ± 3.8 mm in the IA-DEB arm versus the PTA arm, respectively (p = 0.040) documenting significantly deeper wounds in the PTA arm. Professional wound care was received in 62.2% of IA-DEB and 52.1% of PTA patients (p = 0.087), whereas 23.5% of IA-DEB patients and 29.4% of PTA patients received self–wound care (p = 0.248).
Key procedural characteristics
Pre-dilation of the target lesion was performed in 90.5% of patients in the IA-DEB arm and 36.0% of patients in the PTA arm (p < 0.001). Direct revascularization to the wound-related artery was obtained in 35.6% of patients in the IA-DEB arm and 43.7% of patients in the PTA arm (p = 0.166).
Procedural complications did not differ significantly when individually assessed; the aggregate incidence was significantly higher in the IA-DEB arm (9.7%) versus the PTA (3.4%) arm (p = 0.035). Freedom from post-procedural dissection was higher in the IA-DEB (87.7%) versus the PTA (80.8%) arm (p = 0.045) and was primarily mild and non–flow limiting; bailout stenting was performed in 2.3% of IA-DEB patients and 2.8% of PTA patients (p = 0.771). Baseline angiographic and procedural characteristics are described in Table 3. Site-reported Device Success was 98.0% for the IA-DEB arm and 96.3% for the PTA arm (p = 0.224). Site reported Technical Success was 90.8% for the IA-DEB arm and 91.2% for the PTA arm (p = 0.885). Procedural Success was 81.4% for the IA-DEB arm and 79.1% for the PTA arm (p = 0.609).
Primary efficacy results
The 12-month CD-TLR rate was 9.2% in the IA-DEB arm and 13.1% in the PTA arm (p = 0.291) when assessed in the protocol-specified amputation-free surviving population and 11.9% in the PTA arm and 13.5% in the PTA arm (p = 0.682) when assessed in the entire 358-patient population with respective cumulative TLR rates of 15.5% and 20.2% (p = 0.2665). In the 167-patient angiography cohort, there were no differences (p = 0.950) between the IA-DEB arm (0.61 ± 0.78 mm) and the PTA arm (0.62 ± 0.78 mm) in the 12-month angiographic core laboratory assessments of LLL. Furthermore, angiographic core laboratory secondary efficacy analysis at 12-month follow-up showed no differences in binary (≥50% diameter stenosis) restenosis rates (41.0% vs. 35.5%; p = 0.609) and reocclusion rates (11.5% vs. 16.1%; p = 0.531) of the IA-DEB versus the PTA arm, respectively. There were no reported differences in longitudinal restenosis, calculated as the mean ratio (%) between the length of the restenotic (<50% diameter stenosis) lesion and the initial lesion length, between the IA-DEB (99.7 ± 120.2%) and the PTA (88.3 ± 40.5%) arms (p = 0.774). The 12-month primary and secondary efficacy results are described in Table 4.
Primary safety results
The composite of all-cause death, major amputation, and CD-TLR rates through 6 months were 17.7% in the IA-DEB arm and 15.8% in the PTA arm (p = 0.021 for noninferiority). A safety signal driven by major amputation at 12-months was observed, with respective rates of 8.8% and 3.6% (p = 0.080) in the IA-DEB arm and the PTA arm (Figure 2). Major amputation-free survival at 12 months was 81.1% and 89.2% (p = 0.057), respectively, in the IA-DEB and PTA arms. All-cause mortality rates were 10.1% for IA-DEB and 8.1% for PTA (p = 0.551). The combined endpoint, including all-cause death/major or minor amputation rate, was 35.2% for IA-DEB and 25.2% for PTA (p = 0.064). The overall complication rate, a composite of core laboratory-adjudicated incidence of vasospasm, abrupt closure, vessel recoil, thrombus, and perforation, was higher in the IA-DEB arm versus the PTA arm (9.7% vs. 3.4%; p = 0.035); however, these complications were successfully managed and were not associated with a higher incidence of distal embolization or need for provisional stent deployment. Wound healing was reported in 73.8% of IA-DEB patients versus 76.9% of the PTA patients (p = 0.579). Primary and secondary safety results are described in Table 5.
In the IA-DEB and PTA arms, 52.6% and 52.7% of patients were respectively evaluable by the angiographic core laboratory and 40.4% and 53.3% were respectively evaluable by the wound core lab. Most qualifying angiogram losses were the result of subject death, major amputation of the target limb, subject withdrawal, or patient refusal of the angiogram.
Subgroup and multivariate analysis
Rutherford Category indicated no differences in the 6-month primary safety endpoint, the 12-month major amputation or mortality. There were also no differences in the primary efficacy endpoints (Table 6). Additional post hoc subanalyses, including impact of intervention on the wound related artery (direct vs. indirect) or pedal loop status, did not reveal any beneficial subgroups. By post hoc multivariate analysis, confinement to bed with a hazard rate of 3.9 was the only significant factor identified as affecting major amputations within 1 year.
The IN.PACT DEEP trial is a randomized, independently adjudicated post-market trial designed to assess the efficacy and safety of IA-DEB within the CLI population. The trial failed to meet its primary efficacy endpoint of IA-DEB superiority compared to PTA. All lesion-specific primary and secondary endpoints showed insignificant differences between the 2 study arms. Such similar angiographic results were combined with a lower major amputation rate in the PTA arm, despite significantly longer lesions and deeper ulcers in the control arm. This observation further confirms the lack of treatment effect of the study device in reducing restenosis and supports the hypothesis of multiple concomitant factors in the complex chain of CLI therapy, which may have contributed to this difference in clinical outcome. Although the primary safety endpoint was statistically met through a pre-specified noninferiority analysis, secondary safety endpoints including major amputation rate, death, amputations, and amputation-free survival trended against the IA-DEB treatment arm. The observed absence of efficacy superiority compared to PTA and the safety signal resulted in the sponsor’s decision to withdraw the IA-DEB device from the market.
CLI patients are at risk for restenosis and complications arising from progression of the atherosclerotic process. The PTA arm had more favorable efficacy and safety outcomes compared to historical trials; the extraordinarily low 35% 12-month binary restenosis rate and major amputation rate of 3.6% in the PTA arm compare very favorably to previously published data in similar CLI populations treated with PTA alone (17–20). While the IN.PACT DEEP trial may set a new benchmark with standard PTA for the treatment of CLI patients due to the observed extremely low reintervention and amputation rates, alternative therapies, such as drug-eluting stents for short lesions or bypass for longer lesions, may still apply as valuable options in patients who are surgical candidates (11,21) (Central Illustration).
While restenosis of the wound-related artery may result in the failure to heal an ischemic wound, numerous other CLI-related and therapeutic-specific variables challenge the primary role of sustained primary patency on limb preservation and are confounders in interpreting the results of a clinical trial. Factors such as the status of pedal circulation, wound infection/location, and the frequency/quality of podiatric surveillance programs and wound care may either positively compensate for restenosis or negatively impact the persistent patency. Although the IN.PACT DEEP trial is the largest randomized CLI trial to date, its cohort size may be insufficient to adequately reflect the breadth and heterogeneity of the CLI disease spectrum (22,23). More specifically, the trial was not powered to assess major amputation as an endpoint.
The first reported use of IA-DEB for infrapopliteal revascularization originated from a single-center, retrospective, self-adjudicated 104-patient registry (13). Long and complex lesions (mean 17.6 cm, >60% total occlusions) were treated within a mixed population of CLI and severe claudicants resulting in a 3-month angiographic restenosis rate of 27.4% and a 12-month TLR rate of 17.3%. These initial IN.PACT Amphirion restenosis and TLR rates results were a considerable improvement when compared with the 68.8% 3-month restenosis and 50% 1-year TLR rates from a historical PTA cohort of similar baseline characteristics (16). Liistro et al. (14), in a single-center, randomized, self-adjudicated 132-patient trial, also reported significantly lower 12-month restenosis and occlusion rates of 27% versus 74% (p < 0.001) and 17% versus 55% (p < 0.001) in IA-DEB compared to PTA, respectively. The investigators reported reintervention rates of 18% versus 43% (p = 0.002) in a diabetic CLI population with a mean lesion length of 13 cm and 80% occlusive disease (14). The extraordinarily high limb preservation rate reported by Liistro et al., with only 1 major amputation in the PTA arm (despite higher rates of restenosis and reintervention at 1 year), may reflect optimal revascularization outcomes combined with a meticulous wound surveillance program with twice weekly office visits for the first 2 months, office visits once a week for the third month, and then every 2 weeks thereafter. Notably, no standardized protocol to guide wound management was mandated in the IN.PACT DEEP trial participating centers. Wound management was administered according to the individual sites’ standard of care. As previously noted, 23.5% of patients in the IA-DEB arm and 29.4% in the PTA arm received self-administered wound care. The contradictory conclusions of the IN.PACT DEEP trial compared to these 2 studies raise questions as to their methodologies and validity. It is not uncommon for single-center trials to show larger treatment effects or even report opposite outcomes compared to large, multicenter trials (23–27). Besides unavoidable differences in patient populations across trials, systematic (and unmeasured) errors are typical of single-center trials, which may result in superior outcomes that may not be generalized to other, less expert practitioners from lower-volume practice settings.
The reason for the IN.PACT DEEP trial DEB arm’s failure to meet its efficacy endpoint and to report a safety concern remains a point of conjecture. It can be hypothesized that potential disease, device, and/or procedural specific factors might have contributed to the observed lack of drug treatment effect. The observed 2.4-fold higher major amputation rate in the study arm remains the most perplexing data to interpret. It can be speculated that a wide array of factors may contribute to the decision to perform a major amputation, especially when an accepted and standardized definition of “planned major amputation” was not implemented in the trial. Nevertheless, the study sponsor continues to explore all potential causes for the observed lack of efficacy, including the differences in coating methods and balloon materials between the IA-DEB and the other DEBs in the IN.PACT product line indicated for femoropopliteal lesions. In this regard, the negative IN.PACT DEEP study results are contrary to multicenter randomized and single-arm studies (28,29) that have consistently supported the safety and efficacy of IN.PACT DEB for femoropopliteal applications. It is worth noting that the IN.PACT DEEP trial results only apply to the specific IA-DEB study device for BTK revascularization. Positive results on the use of IN.PACT and other DEB technologies have been consistently reported for the femoropopliteal vascular territory, which may likely derive from known differences in the severity of vascular disease and DEB technologies (28,30,31).
In the IN.PACT DEEP trial, operators could not be blinded to the assigned treatment. Moreover, the study protocol did not guide or provide standards for decision-making involving amputation and for the intensity of wound care surveillance and care. Additionally, the low angiographic and wound imaging compliance may have limited the full assessment of this therapy. The subgroup analyses have not explained the divergence of IA-DEB efficacy and safety results compared to prior studies. Overall, these data reflect the challenges of CLI research trials.
This first multicenter, independently-adjudicated, randomized, controlled trial of DEB versus PTA in CLI patients with infrapopliteal disease demonstrated that IA-DEB did not provide a significant reduction in either LLL or CD-TLR revascularization compared to PTA. IA-DEB was associated with a trend toward an increased rate of major amputations through 1 year post-procedure.
COMPETENCY IN MEDICAL KNOWLEDGE: CLI, which includes ischemic lower extremity rest pain, nonhealing ischemic ulcers or gangrene, is the most severe manifestation of PAD and is associated with a high risk of tissue loss, amputation, and cardiovascular mortality. Revascularization by PTA is associated with freedom from major amputation in a high proportion of cases selected on the basis of angiographic pathoanatomy.
COMPETENCY IN PATIENT CARE: In patients with PAD who develop CLI, angiographic assessment of percutaneous revascularization by PTA should be considered to reduce the risk of limb loss.
TRANSLATIONAL OUTLOOK 1: Longer-term follow-up of patients undergoing PTA will more accurately characterize the durability of percutaneous revascularization in patients with CLI.
TRANSLATIONAL OUTLOOK 2: Additional research is needed to define the impact of specific balloon materials, coatings, drug concentrations, and other methodological aspects of PTA on intimal hyperplasia and clinical outcomes when employed in various vascular territories.
The authors wish to acknowledge Martin Faiss, PhD, for critical review of the manuscript, and Victoria Rendon and John Robinson, MD, for assistance in its preparation.
Medtronic, Inc. (Santa Rosa, California) funded this project. Dr. Zeller has received consulting fees from Medtronic, Gore, Cook, Bard, Covidien, Biotronik, and Abbott Vascular; and serves on the advisory board of Medtronic, Boston Scientific, and Gore. Drs. Scheinert, Micari, Kent, and Rocha-Singh have served as consultants for Medtronic. Dr. Vermassen receives grant support from and is a consultant for Medtronic. Mr. Landini and Dr. Snead are Medtronic employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- clinically driven target lesion revascularization
- critical limb ischemia
- drug-eluting balloon
- IN.PACT Amphirion drug-eluting balloon
- late lumen loss
- percutaneous transluminal angioplasty
- target lesion revascularization
- Received April 3, 2014.
- Revision received May 24, 2014.
- Accepted June 24, 2014.
- American College of Cardiology Foundation
- Nolan B.W.,
- De Martino R.R.,
- Stone D.H.,
- et al.,
- for the Vascular Study Group of New England
- Schmidt A.,
- Piorkowski M.,
- Werner M.,
- et al.
- Liistro F.,
- Porto I.,
- Angioli P.,
- et al.
- ↵Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia (INPACT-DEEP). July 16, 2009, updated February 3, 2014. Available at: http://clinicaltrials.gov/show/NCT00941733. Accessed August 4, 2014.
- Zeller T.,
- Baumgartner I.,
- Scheinert D.,
- et al.,
- for the IN.PACT DEEP Trial Investigators
- Scheinert D.,
- Katsanos K.,
- Zeller T.,
- et al.,
- for the ACHILLES Investigators
- Rastan A.,
- Brechtel K.,
- Krankenberg H.,
- et al.
- Werk M.,
- Albrecht T.,
- Meyer D.R.,
- et al.
- Micari A.,
- Cioppa A.,
- Vadalà G.,
- et al.
- Scheinert D.,
- Duda S.,
- Zeller T.,
- et al.