Evaluation of an Infrapopliteal Drug-Eluting Resorbable Scaffold: Design Methodology for the LIFE-BTK Randomized Controlled Trial.

Background: Critical limb-threatening ischemia (CLTI) is a severe condition characterized by rest pain and ischemic tissue loss that affects 5% to 10% of people with peripheral artery disease. In the United States, there are few Food and Drug Administration-approved devices for the primary treatment of arteries below-the-knee (BTK). Unfortunately, all suffer from high restenosis rates due to intimal hyperplasia, elastic recoil, and untreated dissection because of a lack of scaffolding. The Esprit BTK system is a resorbable, drug-eluting scaffold device with the potential to address an unmet need in people suffering from CLTI because of infrapopliteal atherosclerosis. The LIFE-BTK (pivotaL Investigation of saFety and Efficacy of drug-eluting resorbable scaffold treatment-Below The Knee) randomized controlled trial (RCT) is a prospectively designed premarket evaluation of the Esprit BTK drug-eluting resorbable scaffold used in the treatment of those patients. Methods: The LIFE-BTK trial enrolled 261 subjects with CLTI for the RCT and a further 7 subjects for a pharmacokinetic substudy. The objective of the RCT was to evaluate the safety and efficacy of the Esprit BTK scaffold compared to percutaneous transluminal angioplasty. The primary efficacy end point was a composite of limb salvage and primary patency at 12 months. The primary safety end point is freedom from major adverse limb events and peri-operative death at 6 months and 30 days, respectively. Clinical follow-up care is planned for 5 years. Conclusions: Novel devices must be tested in RCTs to evaluate their safety and efficacy compared to the standard of care if we are to improve outcomes for this challenging group of patients.

Long-Term Clinical Effectiveness of a Drug-Coated Balloon for the Treatment of Femoropopliteal Lesions.

Background While randomized trials have demonstrated the superiority of drug-coated balloon (DCB) angioplasty versus standard percutaneous transluminal angioplasty (PTA) in patients with femoropopliteal peripheral artery disease, the long-term durability of DCB angioplasty remains uncertain. Methods and Results IN.PACT SFA is a prospective, multicenter, randomized single-blinded trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 subjects with symptomatic (Rutherford 2-4) femoropopliteal lesions. Subjects were randomly assigned 2:1 to the IN.PACT Admiral DCB or PTA. Assessments through 5 years included freedom from clinically driven target lesion revascularization, the primary safety end point, and major adverse events. Through 5 years, patients treated with the IN.PACT Admiral DCB demonstrated a sustained treatment effect with superior freedom from clinically driven target lesion revascularization when compared with PTA (Kaplan-Meier estimate of 74.5% versus 65.3%; log-rank P=0.020). The primary safety composite was achieved in 70.7% of subjects in the DCB and 59.6% in the PTA groups ( P=0.068). The major adverse event rate was 42.9% for DCB and 48.1% for PTA ( P=0.459). There were no device- or procedure-related deaths in either group as adjudicated by an independent and blinded Clinical Events Committee. Conclusions The IN.PACT SFA randomized trial demonstrates that the IN.PACT Admiral DCB continues to perform better than PTA through 5 years with higher freedom from clinically driven target lesion revascularization. The sustained safety and effectiveness profile of this DCB supports its use as a preferred treatment choice compared with PTA for femoropopliteal lesions. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01175850 (IN.PACT SFA phase I) and NCT01566461 (IN.PACT SFA phase II).

Carotid Stent Fractures Are Not Associated With Adverse Events: Results From the ACT-1 Multicenter Randomized Trial (Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease).

BACKGROUND: The impact of carotid artery stent fractures on the incidence of adverse clinical events remains unclear. The objective of this study is to report the stent fracture rate and its association with in-stent restenosis and adverse outcomes in the ACT-1 trial (Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease). METHODS: ACT-1 is a prospective multicenter trial of patients who have standard surgical risk with severe asymptomatic carotid artery stenosis randomly assigned to carotid artery stenting or carotid endarterectomy (Abbott Vascular). The primary end point was a composite of death, stroke, or myocardial infarction during the 30 days after the procedure or ipsilateral stroke during the 365 days after the procedure. After 771 patients were enrolled, successively randomly assigned patients were required to undergo annual radiographic (x-ray) analysis for stent fracture. Images were independently adjudicated by a core laboratory. RESULTS: Of 1021 patients treated with carotid artery stenting during a mean follow-up of 3.1±1.6 years, 939 had at least 1 x-ray during the follow-up period. Stent fracture was reported in 51 (5.4%) patients. With a maximum follow-up period of 5 years, adverse clinical outcomes occurred in 39 patients with at least 1 x-ray during the follow-up. Of 826 (80.9%) subjects who underwent both duplex ultrasound and x-ray, 822 (99.5%) were interpretable. There was no association between stent fracture and the primary end point (P=0.86) or with restenosis (P=0.53). CONCLUSIONS: In this large, independently adjudicated, multicenter study, the stent fracture rate was low and not associated with major adverse clinical events or in-stent restenosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00106938.

Perioperative Outcomes From the Prospective Multicenter Least Invasive Fast-Track EVAR (LIFE) Registry.

PURPOSE: To determine the feasibility, perioperative resource utilization, and safety of a fast-track endovascular aneurysm repair (EVAR) protocol in well-selected patients. METHODS: Between October 2014 and May 2016, the LIFE (Least Invasive Fast-track EVAR) registry ( ClinicalTrials.gov identifier NCT02224794) enrolled 250 patients (mean age 73±8 years; 208 men) in a fast-track EVAR protocol comprised of bilateral percutaneous access using the 14-F Ovation stent-graft, no general anesthesia, no intensive care unit (ICU) admission, and next-day discharge. The primary endpoint was major adverse events (MAE) through 30 days. The target performance goal for the MAE endpoint was 10.4%. RESULTS: Vascular access, stent-graft delivery, and stent-graft deployment success were 100%. A total of 216 (86%) patients completed all elements of the fast-track EVAR protocol. Completion of individual elements was 98% for general anesthesia avoidance, 97% for bilateral percutaneous access, 96% for ICU avoidance, and 92% for next-day discharge. Perioperative outcomes included mean procedure time of 88 minutes, median blood loss of 50 mL, early oral nutrition (median 6 hours), early mobilization (median 8 hours), and short hospitalization (median 26 hours). Fast-track EVAR completers had shorter procedure time (p<0.001), less blood loss (p=0.04), faster return to oral nutrition (p<0.001) and ambulation (p<0.01), and shorter hospital stay (p<0.001). With 241 (96%) of the 250 patients returning for the 30-day follow-up, the MAE incidence was 0.4% (90% CI 0.1% to 1.8%), significantly less than the 10.4% performance goal (p<0.001). No aneurysm rupture, conversion to surgery, or aneurysm-related secondary procedure was reported. There were no type III endoleaks and 1 (0.4%) type I endoleak. Iliac limb occlusion was identified in 2 (0.8%) patients. The 30-day hospital readmission rate was 1.6% overall. CONCLUSION: A fast-track EVAR protocol was feasible in well-selected patients and resulted in efficient perioperative resource utilization with excellent safety and effectiveness.

Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis.

BACKGROUND: Previous clinical trials have suggested that carotid-artery stenting with a device to capture and remove emboli ("embolic protection") is an effective alternative to carotid endarterectomy in patients at average or high risk for surgical complications. METHODS: In this trial, we compared carotid-artery stenting with embolic protection and carotid endarterectomy in patients 79 years of age or younger who had severe carotid stenosis and were asymptomatic (i.e., had not had a stroke, transient ischemic attack, or amaurosis fugax in the 180 days before enrollment) and were not considered to be at high risk for surgical complications. The trial was designed to enroll 1658 patients but was halted early, after 1453 patients underwent randomization, because of slow enrollment. Patients were followed for up to 5 years. The primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a noninferiority margin of 3 percentage points. RESULTS: Stenting was noninferior to endarterectomy with regard to the primary composite end point (event rate, 3.8% and 3.4%, respectively; P=0.01 for noninferiority). The rate of stroke or death within 30 days was 2.9% in the stenting group and 1.7% in the endarterectomy group (P=0.33). From 30 days to 5 years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stenting group and 97.3% in the endarterectomy group (P=0.51), and the overall survival rates were 87.1% and 89.4%, respectively (P=0.21). The cumulative 5-year rate of stroke-free survival was 93.1% in the stenting group and 94.7% in the endarterectomy group (P=0.44). CONCLUSIONS: In this trial involving asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications, stenting was noninferior to endarterectomy with regard to the rate of the primary composite end point at 1 year. In analyses that included up to 5 years of follow-up, there were no significant differences between the study groups in the rates of non-procedure-related stroke, all stroke, and survival. (Funded by Abbott Vascular; ACT I ClinicalTrials.gov number, NCT00106938.).