Stellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies.

BACKGROUND: Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease. METHODS: In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2-4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable. RESULTS: In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL). CONCLUSIONS: The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.

Tibio-pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: the TAMI technique, original case series.

BACKGROUND: A tibial-pedal access method is needed for patients with advanced peripheral artery disease (PAD) unable to tolerate common femoral artery (CFA) access and intervention due to body habitus or comorbidities. This is the first case series reporting an alternative technique to revascularize such patients. Using ultrasound (US) and the tibio-pedal arterial minimally invasive retrograde revascularization (TAMI) technique, operators accessed, and revascularized the lower extremity completely via tibial-pedal arterial access. METHODS: This retrospective, single-center, case series recorded on 23 patients who underwent TAMI revascularization during a seven-month period in 2012, demonstrating the feasibility and safety of the TAMI technique. Eighty-three percent had Rutherford Classification IV-VI. Ultrasound guidance aided all tibial access. Demographics, vascular symptoms, disease characteristics, success, procedure length, time to discharge, immediate and 30-day complications were collected. Comparison was sought with 201 unmatched patients treated via traditional CFA access over a similar period. RESULTS: Arterial access was successful in all patients. Thirty-six lesions were treated. Lesion success (ability to cross lesion and achieve post treatment stenosis <30%) was achieved in 95% of patients. 25% of lesions were above the knee. Average prestenosis was 92.5%; average poststenosis 12%. No major complications were noted. Two patients presented within 30 days with access site pain. Access site peroneal artery pseudo-aneurysms were diagnosed and treated percutaneously with covered stents. Both recovered with no sequelae. CONCLUSION: Retrograde tibio-pedal intervention appears to be safe and effective. The TAMI technique offers an alternate revascularization method for critically ill advanced PAD patients.

Utility and feasibility of ultrasound-guided access in patients with critical limb ischemia.

BACKGROUND: Patients with advanced peripheral vascular disease (PVD) and critical limb ischemia (CLI) require immediate revascularization to improve blood flow and prevent amputation. Vascular, and especially tibial, access is arguably a very important part of the procedure. Utilization of ultrasound (US) guidance to access the peripheral vessels will maximize success and decrease the risk of complications. METHODS: This is a retrospective analysis of patients admitted to our institution between 2010 and 2011. Eighty-six patients with 191 lesions underwent revascularization for advanced PVD and CLI. US guidance was utilized to access the vascular bed in an antegrade or retrograde fashion in 100% of these patients. Data collected included success rate and time to access using US. Immediate in hospital and 30 day outcomes were also documented. RESULTS: The average age of patients was 69.8 years, with 69.7% male patients. All tibial access (33.7%) was obtained under US guidance. Obtaining vascular access using US was achieved in 95.3% of patients. At discharge, access site complications were limited to one patient (1.1%) with a pseudoaneurysm; no access complications related to the tibial vessels. At 30 days, there was one major amputation (1.1%) and one vascular access complication (1.1%). CONCLUSION: US guided access is a feasible and safe procedure that can aid in accessing vascular conduits in patients with CLI. Applying this technique across the board in CLI patients decreases the risk of immediate complications and facilitates accessing tibial arteries.

Interim Results of the PROMISE I Trial to Investigate the LimFlow System of Percutaneous Deep Vein Arterialization for the Treatment of Critical Limb Ischemia.

OBJECTIVE: To investigate the feasibility, safety, and effectiveness of the LimFlow stent-graft system in performing percutaneous deep vein arterialization (pDVA) for treatment of critical limb ischemia (CLI) patients ineligible for conventional endovascular or surgical revascularization procedures. METHODS: Ten no-option CLI patients (mean age, 67 ± 11 years; 30% women) were enrolled. All patients were classified as Rutherford class 5 or 6 and were deemed by a committee of experts to be ineligible for endovascular or surgical procedures to restore blood flow. Eighty percent were categorized as stage 4 (high risk of amputation) based on Society for Vascular Surgery wound, ischemia, and foot infection (SVS WIfI) scoring index. The primary safety endpoint was amputation-free survival (AFS) at 30 days. A secondary safety endpoint evaluated AFS at 6 months. Other secondary endpoints included primary patency, wound healing, and technical success. RESULTS: Amputation-free survival was achieved in 100% of patients, with no deaths or index limb above-ankle amputations observed at 30 days and 6 months. Technical success rate was 100%. No procedural complications were reported. Primary patency rates at 1 month and 6 months were 90% and 40%, respectively, with reintervention performed in 30% of patients. By 6 months, 30% of patients experienced complete (100%) wound healing, half of patients had 84%-93% wound healing, and 20% of patients experienced 60% healing. CONCLUSION: pDVA using the LimFlow system is a novel approach for treating patients with no-option CLI and may reduce amputation in this population for whom it would otherwise be considered inevitable. Initial findings from this early feasibility trial are promising and additional study is warranted.

Hospital cost impact of orbital atherectomy with angioplasty for critical limb ischemia treatment: a modeling approach.

AIM: The incremental cost of peripheral orbital atherectomy system (OAS) plus balloon angioplasty (BA) versus BA-only for critical limb ischemia was estimated. MATERIALS & METHODS: A deterministic simulation model used clinical and healthcare utilization data from the CALCIUM 360° trial and current cost data. Incremental cost of OAS + BA versus BA-only included differential utilization during the procedure and adverse-event costs at 3, 6 and 12-months. RESULTS: For every 100 procedures, incremental annual costs to the hospital were US$350,930 lower with OAS + BA compared with BA-only. Despite higher upfront costs, savings were realized due to reduced need for revascularization, amputation and end-of-life care over 6-12-month postoperative period. CONCLUSION: Atherectomy with OAS prior to BA was associated with cost savings to the hospital.

Lack of Association Between Limb Hemodynamics and Response to Infrapopliteal Endovascular Therapy in Patients With Critical Limb Ischemia.

BACKGROUND: Non-invasive limb hemodynamics may aid in diagnosis of critical limb ischemia (CLI), although the relationship with disease severity and response to endovascular therapy is unclear. METHODS AND RESULTS: This prospective, single-center study enrolled 100 CLI patients (Rutherford class 4-6) who underwent infrapopliteal endovascular revascularization (175 lesions) in the Peripheral RegIstry of Endovascular Clinical OutcoMEs (PRIME) registry. Hemodynamic measures included ankle-brachial index (ABI), toe-brachial index (TBI), and toe pressure (TP). Procedure success following revascularization was defined as stenosis ≤30%. Hemodynamic success was defined as an increase >0.15 in ABI or TBI relative to baseline. Freedom from amputation was defined as no major or minor amputation during follow-up. Clinical success was defined as a decrease of at least one Rutherford class during follow-up. Treatment success was defined as procedure success, freedom from amputation, and clinical improvement. Median baseline hemodynamic values were 0.90 for ABI, 0.39 for TBI, and 54 mm Hg for TP. Twenty-nine patients (29%) did not meet the common hemodynamic diagnostic criterion for eligibility in CLI trials (ABI ≤0.5, TBI ≤0.5, or TP <50 mm Hg). Main outcomes included 96% procedure success, 95% freedom from amputation, 64% clinical success, and 62% treatment success. There was no relationship between baseline (or with the pretreatment to posttreatment change) limb hemodynamic values and the response to infrapopliteal endovascular therapy. CONCLUSION: Non-invasive hemodynamic studies may have limited clinical usefulness in patients with CLI. The usefulness of these parameters to confirm eligibility and to assess response to therapy in interventional CLI clinical trials should be re-evaluated.

Explaining Racial Disparities in Amputation Rates for the Treatment of Peripheral Artery Disease (PAD) Using Decomposition Methods.

INTRODUCTION: While studies have documented racial and ethnic disparities in amputation rates for patients with peripheral artery disease (PAD), the importance of specific factors has not been quantified. This research seeks to provide such evidence and to quantify how much of the difference reflects observable versus unexplained factors. METHODS: This study used the nationally representative HCUP inpatient database from 2006 to 2013 for patients with a primary diagnosis of PAD who were either Caucasian, African-American, or Hispanic. Multivariable logistic regression models were estimated to identify the determinants of amputation rates. RESULTS: Multivariable results revealed that African-Americans and Hispanics are approximately twice as likely to be amputated as are Caucasians. Observed factors in the models collectively account for 51 to 55 % of the disparities for African-Americans and 64 to 69 % for Hispanics. The results suggest that African-Americans and Hispanics have less access to care, because they are being admitted when sicker and more likely on an emergent basis. CONCLUSIONS: Racial and ethnic disparities in amputation rates are substantial, with disease severity and hospital admission source being key factors.

Percutaneous Transluminal Angioplasty in Patients With Infrapopliteal Arterial Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Contemporary outcomes of percutaneous transluminal angioplasty for the treatment of infrapopliteal atherosclerotic lesions are not well characterized. Hence, a systematic review and meta-analysis was performed to determine the safety and effectiveness of this approach in patients with advanced below-the-knee arterial disease. METHODS AND RESULTS: MEDLINE and EMBASE databases were searched for contemporary studies (2005-2015) on the effects of percutaneous transluminal angioplasty for the treatment of infrapopliteal lesions. A random effects meta-analysis model was used to analyze procedural (technical success, flow-limiting dissection, provisional stent placement) and long-term (primary patency, repeat revascularization, major amputation, all-cause mortality) outcomes. Ultimately, 52 studies encompassing 6769 patients with 9399 below-the-knee lesions were included in the analysis. Technical success was 91.1% (95% confidence interval [CI], 88.8-93.0), and the incidence of flow-limiting dissections and bailout stenting was 5.6% (95% CI, 3.2-9.8) and 9.1% (95% CI, 6.3-12.9), respectively. Outcomes at 1 year were primary patency, 63.1% (95% CI, 57.3-68.6); repeat revascularization, 18.2% (95% CI, 14.5-22.6); major amputation, 14.9% (95% CI, 12.3-18.0); and all-cause mortality, 15.1% (95% CI, 12.8-17.7). Significant heterogeneity and publication bias were observed for most percutaneous transluminal angioplasty outcomes. CONCLUSIONS: Contemporary studies of the use of percutaneous transluminal angioplasty as primary treatment for patients with infrapopliteal arterial disease reveal suboptimal procedural and 1-year clinical outcomes.

Ultrasound-Guided Arterial Access: Outcomes Among Patients With Peripheral Artery Disease and Critical Limb Ischemia Undergoing Peripheral Interventions.

OBJECTIVE: Arterial cannulation is a vital component of endovascular interventions and often unconventional access approaches are required due to disease complexity. Historically, varying maneuvers have been utilized to obtain arterial access. Lack of consensus exists regarding the safest and most effective method. This study examined the feasibility and immediate outcomes of ultrasound-guided access in traditional and advanced access approaches. METHODS: Data were analyzed from a cohort of 407 patients enrolled in the Peripheral RegIstry of Endovascular Clinical OutcoMEs (PRIME). The 407 patients underwent 649 procedures with 896 access sites utilized. Access success, immediate outcomes, complications, and length of hospital stay were analyzed. RESULTS: Mean age was 70 years, and 67% were male. The majority of patients had critical limb ischemia (58%), 39% were Rutherford classification III. Most commonly utilized access sites were common femoral retrograde, common femoral antegrade, posterior tibial, and anterior tibial arteries (34.6%, 33.0%, 12.1%, and 12.1%, respectively). Mean number of attempts was 1.2, 1.2, 1.5, and 1.4, respectively; median time to access was 39, 45, 41, and 59 seconds, respectively; and access success rate was 99.4%, 97.3%, 90.7%, and 92.6%; respectively. Access-site combinations utilized were femoral antegrade (n = 188), femoral retrograde (n = 185), dual femoral/ tibio-pedal (n = 130), dual femoral retrograde (n = 44), retrograde tibio-pedal (n = 73), and other (n = 29). Access-related complications were low overall: hematoma (1.2%), bleeding requiring transfusion/intervention (1.7%), pseudoaneurysm (1.7%), arteriovenous fistula (0.3%), aneurysm (0%), compartment syndrome (0%), and death (0%). CONCLUSION: Utilization of ultrasound-guided arterial access in this complex cohort was shown to be safe and effective regardless of arterial bed and approach.

Balloon angioplasty in tibioperoneal interventions for patients with critical limb ischemia.

Tibial arterial disease represents the final frontier in the battle against critical limb ischemia (CLI). Isolated infrapopliteal (IP) disease is mainly seen in the elderly (>80 years old), diabetic, and dialysis-dependent patients with CLI. With the development and evolution of catheter-based technology, endovascular therapy (mainly balloon angioplasty) has become the method of choice for revascularization in these patients. The most common challenges are the severely calcified lesion recalcitrant to dilation (as calcium is heterogeneously distributed in the arterial wall) and the long tibial chronic total occlusions. Percutaneous transluminal angioplasty achieves a technically successful result (<30% residual stenosis) in most cases, but it is limited by high restenosis rates. Although several devices have been used in the IP arena (including orbital and directional atherectomy, laser atherectomy, "contact" atherectomy [CROSSER, Bard], and re-entry devices), percutaneous transluminal angioplasty with plain old balloons has been the subject of most studies with several modified iterations, that is, cryoplasty, cutting balloons, focal force balloons, nitinol-"cage"-constrained balloons, tapered balloons, and most recently drug-coated balloons. In this article, we share our current approach to endovascular IP endovascular interventions. We cover the spectrum from pathophysiology, clinical indications, equipment choices, and procedural steps used in our laboratory when treating patients with CLI (which is synonymous with complex anatomy). Regarding what represents the "gold standard" for the treatment of IP disease, a definite answer is currently not available, as multiple studies looking at new generation drug-coated balloons used alone or in combination with different forms of atherectomy are currently under way. We anxiously wait for these results and in the meantime continue to design newer approaches.