Mortality and Paclitaxel-Coated Devices: An Individual Patient Data Meta-Analysis.

BACKGROUND: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. METHODS: Manufacturers of US Food and Drug Administration-approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. RESULTS: A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%-58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose-mortality association was identified. CONCLUSIONS: This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.

Directional atherectomy before paclitaxel coated balloon angioplasty in complex femoropopliteal disease: The VIVA REALITY study.

BACKGROUND: Drug coated balloon (DCB) angioplasty significantly reduces reintervention rates in patients with symptomatic femoropopliteal peripheral artery disease (PAD). However, stand-alone DCB use in long, severely calcified lesions is frequently associated with vessel recoil and/or high-grade dissections necessitating provisional stent implantation. OBJECTIVES: Assess the safety and effectiveness of a vessel preparation strategy with directional atherectomy (DA) prior to DCB angioplasty in patients with symptomatic severely calcified femoropopliteal PAD. METHODS: REALITY (NCT02850107) prospectively enrolled subjects at 13 multinational centers with 8-36 cm femoropopliteal stenoses or occlusions with bilateral vessel wall calcification treated with DA prior to DCB angioplasty. The primary effectiveness endpoint was 12-month primary patency, and the primary safety endpoint was freedom from major adverse events through 30 days. Independent angiographic and duplex core laboratories assessed outcomes and a Clinical Events Committee adjudicated events. RESULTS: A total of 102 subjects were enrolled; one lesion was treated per subject. The mean lesion length was 17.9 ± 8.1 cm, 39.0% were chronic total occlusions (mean lesion length 22.6 ± 8.6 cm); 86.2% of lesions exhibited moderate to severe bilateral calcification. Provisional stents were implanted in 8.8% (9/102) of subjects. Twelve-month primary patency rate was 76.7% (66/86) and freedom from CD-TLR rate was 92.6% (87/94). No device or procedure related deaths and one index-limb major amputation were reported. CONCLUSIONS: Plaque excision with DA in patients with symptomatic severely calcified femoropopliteal arterial disease prior to DCB angioplasty is a safe and effective treatment strategy with a low provisional stent rate.

Three-Year Outcomes From the LIBERTY 360 Study of Endovascular Interventions for Peripheral Artery Disease Stratified by Rutherford Category.

PURPOSE: To report the 3-year results of the LIBERTY 360 study, which investigated outcomes of endovascular treatment of symptomatic peripheral artery disease (PAD). MATERIALS AND METHODS: The LIBERTY trial (ClinicalTrials.gov identifier NCT01855412) was a prospective, observational, core laboratory-assessed, multicenter study of endovascular interventions enrolling >1200 participants treated at 51 sites. Data from 1189 patients were stratified according to Rutherford category (RC) and analyzed [RC 2-3 (n=500), RC 4-5 (n=589), and RC 6 (n=100)]. The primary outcomes were major amputation of the target limb and all-cause death; secondary outcomes were target vessel revascularization (TVR) or target lesion revascularization (TLR); major adverse events (MAEs; death within 30 days, TVR or TLR, and major amputation); death or major amputation combined; and change in self-reported quality of life (QoL) measures (VascuQol-25). The Kaplan-Meier (KM) method was employed to estimate the outcomes; estimates are presented with the 95% confidence intervals (CI). Predictors of 3-year MAE, death, TVR, and major amputation were analyzed using Cox proportional hazard regression modeling. RESULTS: The 36-month KM survival rates were 86.0% in RC 2-3, 79.8% in RC 4-5, and 62.0% in RC 6 groups. The KM estimates of freedom from major amputation at 36 months were 98.5% in RC 2-3, 94.0% in RC 4-5, and 79.9% in RC 6. The 36-month KM estimates for freedom from TVR/TLR were 71.1% in RC 2-3, 64.2% in RC 4-5 and 61.9% in RC 6 groups. Patients with claudication at baseline were at lower risk for MAEs compared with RC 4-5 and RC 6 patients during the 36-month follow-up. Vascular QoL improved from baseline and persisted up to 36 months in all patients. CONCLUSION: Endovascular therapy is a viable treatment option for patients with symptomatic PAD, with sustained improved quality of life in both claudicants and patients with chronic limb-threatening ischemia. These results provide important point estimates for midterm outcomes after modern endovascular interventions for PAD.

Mortality Assessment of Paclitaxel-Coated Balloons: Patient-Level Meta-Analysis of the ILLUMENATE Clinical Program at 3 Years.

BACKGROUND: A recent summary-level meta-analysis comprising randomized, controlled trials (RCTs) of femoropopliteal paclitaxel-coated balloon and stent intervention identified excess late mortality in the paclitaxel-treated patients. METHODS: We evaluated the safety of the Stellarex drug-coated balloon (DCB) for femoropopliteal artery disease with an independently performed meta-analysis of patient-level data from all patients in the Stellarex femoropopliteal clinical program. To compare mortality after DCB or uncoated percutaneous transluminal angioplasty (PTA), we aggregated data from 2 RCTs comprising 419 patients treated with DCB and 170 patients treated with PTA. In an additional analysis, data were aggregated from 6 poolable Stellarex DCB studies (2 RCTs, 3 single-arm studies, and 1 registry). All serious adverse events including deaths were adjudicated by a blinded, third-party, independent Clinical Events Committee. Kaplan-Meier estimates in the RCTs were compared with restricted mean survival time. Predictors of death were assessed with hazard ratios (HRs) and Cox proportional hazards modeling. RESULTS: Baseline characteristics were similar in the patients treated with DCB and PTA in the pooled RCT analysis, with the exception that the DCB cohort was younger (67.4±9.7 versus 69.4±9.4 years, P=0.02), smoked more frequently (86.6% versus 78.8%, P=0.02), and were less often treated for recurrent lesions (8.8% versus 14.7%, P=0.04). In the RCTs, patients treated with DCB had all-cause mortality rates that were not different from those of patients treated with PTA (Kaplan-Meier estimates 1.8±0.7% versus 1.3±0.9%, 6.5±1.2% versus 5.9±1.9%, and 9.3±1.5% versus 9.9±2.4% at 1, 2, and 3 years, respectively, P=0.86). All-cause mortality rates were similar in a 1906-patient pooled nonrandomized DCB data set (Kaplan-Meier estimates of 2.1%, 4.9%, and 7.0% at 1, 2, and 3 years, respectively). Clinical Events Committee-adjudicated causes of death were balanced between the DCB and PTA cohorts. Multivariable Cox modeling identified age (HR, 1.06; 95% CI, 1.04-1.08; P<0.001), diabetes mellitus (HR, 1.42; 95% CI, 1.01-2.00; P=0.04), congestive heart failure (HR, 1.88; 95% CI, 1.12-3.16; P=0.02), and renal insufficiency (HR, 2.00; 95% CI, 1.33-3.01; P<0.001) as predictors of mortality. Paclitaxel exposure was unrelated to mortality (HR, 1.04; 95% CI, 0.98-1.10; P=0.23). CONCLUSIONS: The mortality rates for patients treated with the DCB and uncoated PTA were indistinguishable over 3-year follow-up. Additional patient-level, adequately powered meta-analyses with larger RCT data sets will be needed to confirm the generalizability of these findings. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110524, NCT01858363, NCT01858428, NCT03421561, NCT01912937, NCT01927068, and NCT02769273.

Paclitaxel exposure: Long-term safety and effectiveness of a drug-coated balloon for claudication in pooled randomized trials.

BACKGROUND: Paclitaxel drug-coated balloons (DCB) prevent recurrent claudication after angioplasty, yet data from randomized trials with incomplete follow-up have raised uncertainty regarding long-term mortality. OBJECTIVES: To evaluate the effect of paclitaxel exposure on the long-term safety and efficacy of angioplasty of femoropopliteal artery lesions in the combined IN.PACT randomized trials. METHODS: The IN.PACT randomized trials (SFA, N = 331 and Japan, N = 100) each compared the DCB with standard percutaneous transluminal angioplasty (PTA) for claudication, and consented patients for 5 and 3 years, respectively. To address long-term safety, sites were requested to obtain vital status follow-up. In the pooled, updated data set, we examined the association between randomized treatment and mortality by cumulative incidence and hazard ratio (HR), and freedom from clinically driven target lesion revascularization (CD-TLR). Multivariable Cox regression with adjustment for baseline characteristics was used to evaluate the dose effect. Causes of death were adjudicated by a blinded clinical events committee that included oncologists with paclitaxel expertise. RESULTS: The rate of long-term vital status ascertainment increased from 81% to 97% for DCB and from 85% to 97% for PTA in the IN.PACT SFA trial. The cumulative incidence of mortality was 14.7% DCB versus 12.0% PTA at 5 years, HR 1.39, log-rank p = .286. Paclitaxel dose (mg) was not an independent predictor of mortality (HR 1.02, p = .381), but was an independent predictor of reduced risk of CD-TLR (HR 0.79; p < .001). Causes of death did not differ by treatment arm. CONCLUSIONS: In pooled randomized trial data with updated vital status ascertainment, paclitaxel was associated with improved efficacy but was not associated with increased mortality.

Final Two-Year Outcomes for the Sentry Bioconvertible Inferior Vena Cava Filter in Patients Requiring Temporary Protection from Pulmonary Embolism.

PURPOSE: To report final 2-year outcomes with the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). MATERIALS AND METHODS: In a prospective multicenter trial, the Sentry filter was implanted in 129 patients with documented deep vein thrombosis (DVT) and/or PE (67.5%) or who were at temporary risk of developing DVT/PE (32.6%). Patients were monitored and bioconversion status ascertained by radiography, computed tomography (CT), and CT venography through 2 years. RESULTS: The composite primary 6-month endpoint of clinical success was achieved in 97.4% (111/114) of patients. The rate of new symptomatic PE was 0% (n = 126) through 1 year and 2.4% (n = 85) through the second year of follow-up, with 2 new nonfatal cases at 581 and 624 days that were adjudicated as not related to the procedure or device. Two patients (1.6%) developed symptomatic caval thrombosis during the first month and underwent successful interventions without recurrence. No other filter-related symptomatic complications occurred through 2 years. There was no filter tilting, migration, embolization, fracture, or caval perforation and no filter-related deaths through 2 years. Filter bioconversion was successful for 95.7% (110/115) of patients at 6 months, 96.4% (106/110) of patients at 12 months, and 96.5% (82/85) of patients at 24 months. Through 24 months of follow-up, there was no evidence of late-stage IVC obstruction or thrombosis after filter bioconversion or of thrombogenicity associated with retracted filter arms. CONCLUSIONS: The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 2 years of follow-up.

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.

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.).

Design and rationale of a randomized noninferiority trial to evaluate the SurVeil drug-coated balloon in subjects with stenotic lesions of the femoropopliteal artery - the TRANSCEND study.

BACKGROUND: Drug-coated balloons (DCBs), developed to reduce restenosis after percutaneous intervention in peripheral arterial disease (PAD), have been shown to be safe and efficacious, particularly in treating PAD affecting the femoropopliteal segment. The SurVeil DCB uses an excipient intended to optimize both the uniformity and transfer of paclitaxel to the vessel wall, allowing for efficient drug loading and lower systemic exposure than currently available DCBs, Heretofore, clinical outcomes have not previously been compared to other DCBs. STUDY DESIGN AND OBJECTIVES: This prospective, multicenter, international, randomized, single-blind, trial will compare 1:1 the SurVeil DCB with the IN.PACT Admiral DCB for treatment of patients with Rutherford classification 2 to 4 due to femoral and/or popliteal arterial disease. The trial will randomize 446 subjects (with reference vessel diameter 4-7 mm and total lesion length ≤180 mm). Subjects will be followed for 60 months. The primary efficacy endpoint is 1 year primary patency, defined as composite freedom from clinically-driven target-lesion revascularization (TLR) and binary restenosis (core lab-adjudicated duplex ultrasound peak systolic velocity ratio ≥2.4, or ≥50% stenosis via angiography). The primary safety endpoint is composite freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinically-driven target vessel revascularization through 12 months. The primary analysis is a test of noninferiority of the SurVeil vs. IN.PACT Admiral on the primary efficacy and safety endpoints according to absolute deltas of 15.0% and 10.0%, respectively. CONCLUSION: The Randomized And Controlled Noninferiority Trial to Evaluate Safety and Clinical Efficacy of the SurVeil DCB in the Treatment of Subjects with Stenotic Lesions of the Femoropopliteal Artery Compared to the Medtronic IN.PACT Admiral (TRANSCEND) study will assess safety and efficacy of the SurVeil DCB relative to a commonly used DCB.

Pedal access: Put the "pedal to the metal" or drive with caution?

Pedal artery access is associated with few acute complications. Pedal access differs from radial access by often being and associated with the atherosclerotic process being treated. Long-term patency of pedal artery access is necessary before routine adoption.

One-Year Results of the LIBERTY 360 Study: Evaluation of Acute and Midterm Clinical Outcomes of Peripheral Endovascular Device Interventions.

PURPOSE: To report the 1-year results of a multicenter study of peripheral artery disease (PAD) treatment with a variety of endovascular treatment strategies employed in routine practice. MATERIALS AND METHODS: The LIBERTY trial ( ClinicalTrials.gov identifier NCT01855412) is a prospective, observational, core laboratory-assessed, multicenter study of endovascular device intervention in 1204 subjects (mean age 69.8±10.7 years; 770 men) stratified by Rutherford category (RC): claudicants (RC2,3; n=501) and critical limb ischemia (CLI) with no/minimal tissue loss (RC4,5; n=603) or significant tissue loss (RC6; n=100). Key outcomes included quality of life (QoL) measures (VascuQol and EuroQol) and freedom from major adverse events (MAE), defined as death (within 30 days), major amputation, and target vessel revascularization based on Kaplan-Meier analysis. RESULTS: Successful revascularization was beneficial, with RC improvement noted across all groups. Thirty-day freedom from MAE estimates were high across all groups: 99.2% in RC2,3, 96.1% in RC4,5, and 90.8% in RC6. At 12 months, the freedom from MAE was 82.6% in RC2,3, 73.2% in RC4,5, and 59.3% in RC6 patients. Estimates for freedom from major amputation at 12 months were 99.3%, 96.0%, and 81.7%, respectively. QoL scores improved significantly across all domains in all groups with 12-month VascuQol total scores of 5.3, 5.0, and 4.8 for RC2,3, RC4,5, and RC6, respectively. CONCLUSION: The results indicate that peripheral endovascular intervention is a viable treatment option for RC2,3, RC4,5, and RC6 patients as evidenced by the high freedom from major amputation, as well as the improvement in QoL and the RC at 12 months. Furthermore, primary unplanned amputation is often not necessary in RC6.

iCAST Balloon-Expandable Covered Stent for Iliac Artery Lesions: 3-Year Results from the iCARUS Multicenter Study.

PURPOSE: To evaluate safety and effectiveness of the iCAST Covered Stent for treatment of iliac artery atherosclerotic lesions. MATERIALS AND METHODS: The iCARUS trial (ClinicalTrials.gov Identifier: NCT00593385) was a single-arm, prospective, multicenter study that enrolled 152 per protocol subjects at 25 sites in the United States and Germany. Subjects with multiple lesions and/or stents were eligible. The primary endpoint was the composite rate of death within 30 days, target lesion revascularization (TLR) within 9 months, or restenosis at 9 months after procedure. Secondary endpoints included major adverse vascular events (MAVEs), primary patency, freedom from TLR, and clinical success. RESULTS: Device and acute procedural success were achieved in 98.7% and 92.7% of cases, respectively. MAVE rate was 4.6% at 30 days. The 9-month primary composite endpoint rate was 8.1% (10/123), which was below the performance goal of 16.57%. Nine-month primary patency, defined as continuous flow without revascularization, bypass, or target limb amputation, was 96.4%. Freedom from TLR at 9 months and 3 years was 97.2% and 86.6%, respectively. Early clinical success was seen in 88.7% of subjects at 30 days with sustained clinical benefit in 72.4% of subjects at 3 years. CONCLUSIONS: The iCARUS study demonstrated that the iCAST Covered Stent was safe and effective for treatment of atherosclerotic iliac artery lesions with sustained clinical benefit out to 3 years.

A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease With a Focus on Revascularization: A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative.

Peripheral artery disease affects >200 million people worldwide and is associated with significant limb and cardiovascular morbidity and mortality. Limb revascularization is recommended to improve function and quality of life for symptomatic patients with peripheral artery disease with intermittent claudication who have not responded to medical treatment. For patients with critical limb ischemia, the goals of revascularization are to relieve pain, help wound healing, and prevent limb loss. The baseline risk of cardiovascular and limb-related events demonstrated among patients with stable peripheral artery disease is elevated after revascularization and related to atherothrombosis and restenosis. Both of these processes involve platelet activation and the coagulation cascade, forming the basis for the use of antiplatelet and anticoagulant therapies to optimize procedural success and reduce postprocedural cardiovascular risk. Unfortunately, few high-quality, randomized data to support use of these therapies after peripheral artery disease revascularization exist, and much of the rationale for the use of antiplatelet agents after endovascular peripheral revascularization is extrapolated from percutaneous coronary intervention literature. Consequently, guideline recommendations for antithrombotic therapy after lower limb revascularization are inconsistent and not always evidence-based. In this context, the purpose of this structured review is to assess the available randomized data for antithrombotic therapy after peripheral arterial revascularization, with a focus on clinical trial design issues that may affect interpretation of study results, and highlight areas that require further investigation.

Endovascular baroreflex amplification for resistant hypertension: a safety and proof-of-principle clinical study.

BACKGROUND: Carotid baroreflex activation lowers blood pressure and might have potential application for the treatment of resistant hypertension. We did a proof-of-principle trial with a novel endovascular baroreceptor amplification device, MobiusHD (Vascular Dynamics, Mountain View, CA, USA), in patients with resistant hypertension. METHODS: CALM-FIM_EUR was a prospective, first-in-human, open-label study done at six European centres. Eligible patients were adults with resistant hypertension (office systolic blood pressure ≥160 mm Hg despite taking at least three antihypertensive agents, including a diuretic). MobiusHD devices were implanted unilaterally in the internal carotid artery. The primary endpoint was the incidence of serious adverse events at 6 months. Secondary endpoints included changes in office and 24 h ambulatory blood pressure. This trial is registered with ClinicalTrials.gov, number NCT01911897. FINDINGS: Between December, 2013, and February, 2016, 30 patients were enrolled and underwent successful implantation. Mean age was 52 years (SD 12), 15 patients (50%) were men, and mean antihypertensive use was 4·4 drugs (1·4). Mean office blood pressure was 184/109 mm Hg (18/14) at baseline and was reduced by 24/12 mm Hg (13-34/6-18) at 6 months (p=0·0003 for systolic and p=0·0001 diastolic blood pressure). Mean baseline 24 h ambulatory blood pressure was 166/100 mm Hg (17/14) at baseline and was reduced by 21/12 mm Hg (14-29/7-16) at 6 months (p<0·0001 for systolic and diastolic blood pressure). Five serious adverse events had occurred in four patients (13%) at 6 months: hypotension (n=2), worsening hypertension (n=1), intermittent claudication (n=1) and wound infection (n=1). INTERPRETATION: In patients with resistant hypertension, endovascular baroreceptor amplification with the MobiusHD device substantially lowered blood pressure with an acceptable safety profile. Randomised, double-blind, sham-controlled trials are warranted to investigate the use of this treatment further. FUNDING: Vascular Dynamics.

Full Drug-Eluting Stent Jacket: Two-Year Results of a Single-Center Experience With Zilver PTX Stenting for Long Lesions in the Femoropopliteal Arteries.

PURPOSE: To evaluate the 1- and 2-year patency and reintervention rates with the Zilver PTX drug-eluting stent (DES) in long complex femoropopliteal disease. METHODS: A retrospective review was conducted of 89 consecutive patients (mean age 68.7±9.8 years; 86 men) with femoropopliteal occlusive disease (Rutherford category 2-6) treated with the Zilver PTX between December 2012 and December 2013. Mean lesion length for the entire cohort was 24.2±11.3 cm (median 24.0, range 4-48). The patient population was dichotomized into a short lesion (≤20 cm) group (n=41; mean lesion length 13.3±5.6 cm) and the full DES jacket (>20 cm) group (n=48; mean lesion length 33.0±6.5 cm). Primary endpoints were duplex-derived restenosis (peak systolic velocity ratio >2.5), clinically driven reintervention, and major amputation. RESULTS: The incidence of restenosis was lower in the short lesion group at 1 year (19% vs 40% for the longer lesions, p=0.050) and 2 years (39% vs 54%, respectively; p=0.331). The short lesion group had significantly lower rates of reintervention at both 1 year (2% vs 21% in long lesions, p=0.009) and 2 years (12% vs 33%, p=0.019). CONCLUSION: Treatment of femoropopliteal lesions >20 cm with the Zilver PTX appears to be a clinically effective therapy for patients with symptomatic peripheral artery disease. However, there is an increase in restenosis and a need for reintervention that continues to progress up to 2 years.

Drug-Coated Balloon Treatment of Femoropopliteal Lesions Typically Excluded From Clinical Trials: 12-Month Findings From the IN.PACT Global Study.

PURPOSE: To report a post hoc analysis comparing outcomes between subjects who would have been included in the IN.PACT SFA randomized controlled trial vs those who would have been excluded. METHODS: The 1406 subjects enrolled in the IN.PACT Global Study ( ClinicalTrials.gov identifier NCT01609296) were retrospectively assigned to a standard-use group (n=281) based on the inclusion and exclusion criteria from the randomized IN.PACT SFA trial; the remaining 1125 patients were assigned to the broader-use group. Freedom from clinically-driven target lesion revascularization (CD-TLR) was evaluated at 12 months. The composite primary safety endpoint was freedom from 30-day device- and procedure-related death plus freedom from 12-month target limb major amputation and clinically-driven target vessel revascularization (CD-TVR). Functional outcomes were evaluated with dedicated questionnaires. RESULTS: Compared with the standard-use cohort, the broader-use lesions were longer, more calcified, and had more popliteal involvement, bilateral disease, and in-stent restenosis (p<0.001 for all). Freedom from 12-month CD-TLR by Kaplan-Meier analysis was 96.6% for the standard-use group and 91.6% for the broader-use group (p=0.005). The safety endpoint was 96.2% in the standard-use group and 91.0% in the broader-use group (p=0.003). The 12-month CD-TLR (3.4% standard-use vs 8.5% broader-use, p=0.004) and CD-TVR (4.2% standard-use vs 9.1% broader-use, p=0.008) were increased in the broader-use group. Twelve-month all-cause mortality was not increased (3.8% standard-use vs 3.4% broader-use, p=0.852). CONCLUSION: Post hoc analysis of the IN.PACT Global Study of real-world patients demonstrated consistent outcomes with significant clinical improvement to 12 months in subjects with complex lesions typically excluded from a randomized controlled trial.

Edoxaban Plus Aspirin vs Dual Antiplatelet Therapy in Endovascular Treatment of Patients With Peripheral Artery Disease: Results of the ePAD Trial.

PURPOSE: To report a randomized study that investigated the safety (risk of major bleeds) and potential efficacy of edoxaban, an oral anticoagulant that targets the major components of arterial thrombi, to prevent loss of patency following endovascular treatment (EVT). METHODS: Between February 2012 and June 2014, 203 patients who underwent femoropopliteal EVT were randomized to receive aspirin plus edoxaban or aspirin plus clopidogrel for 3 months in the Edoxaban in Peripheral Arterial Disease (ePAD) study ( ClinicalTrials.gov identifier NCT01802775). Randomization assigned 101 patients (mean age 68.0±10.4 years; 67 men) to the edoxaban group and 102 patients (mean age 66.7±8.6 years; 78 men) to the clopidogrel group. The primary safety endpoint was bleeding as classified by the TIMI (Thrombolysis in Myocardial Infarction) criteria and ISTH (International Society of Thrombosis and Hemostasis) criteria; the efficacy endpoint was the rate of restenosis/reocclusion. RESULTS: There were no major or life-threatening bleeding events in the edoxaban group, while there were 2 major and 2 life-threatening bleeding events in the clopidogrel group by the TIMI criteria. By the ISTH classification, there was 1 major and 1 life-threatening bleeding event vs 5 major and 2 life-threatening bleeding events, respectively [relative risk (RR) 0.20, 95% confidence interval (CI) 0.02 to 1.70]. The bleeding risk was not statistically different with either treatment when assessed by TIMI or ISTH. Following 6 months of observation, there was a lower incidence of restenosis/reocclusion with edoxaban compared with clopidogrel (30.9% vs 34.7%; RR 0.89, 95% CI 0.59 to 1.34, p=0.643). CONCLUSION: These results suggest that patients who have undergone EVT have similar risks for major and life-threatening bleeding events with edoxaban and aspirin compared with clopidogrel and aspirin. The incidence of restenosis/reocclusion events, while not statistically different, was lower with edoxaban and aspirin, but an adequately sized trial will be needed to confirm these findings.

One-Year Analysis of the Prospective Multicenter SENTRY Clinical Trial: Safety and Effectiveness of the Novate Sentry Bioconvertible Inferior Vena Cava Filter.

PURPOSE: To prospectively assess the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). MATERIALS AND METHODS: At 23 sites, 129 patients with documented deep vein thrombosis (DVT) or PE, or at temporary risk of developing DVT or PE, unable to use anticoagulation were enrolled. The primary end point was clinical success, including successful filter deployment, freedom from new symptomatic PE through 60 days before filter bioconversion, and 6-month freedom from filter-related complications. Patients were monitored by means of radiography, computerized tomography (CT), and CT venography to assess filtering configuration through 60 days, filter bioconversion, and incidence of PE and filter-related complications through 12 months. RESULTS: Clinical success was achieved in 111 of 114 evaluable patients (97.4%, 95% confidence interval [CI] 92.5%-99.1%). The rate of freedom from new symptomatic PE through 60 days was 100% (n = 129, 95% CI 97.1%-100.0%), and there were no cases of PE through 12 months for either therapeutic or prophylactic indications. Two patients (1.6%) developed symptomatic caval thrombosis during the first month; neither experienced recurrence after successful interventions. There was no filter tilting, migration, embolization, fracture, or caval perforation by the filter, and no filter-related death through 12 months. Filter bioconversion was successful for 95.7% (110/115) at 6 months and for 96.4% (106/110) at 12 months. CONCLUSIONS: The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 12 months of imaging-intense follow-up.

Design Strategies for Global Clinical Trials of Endovascular Devices for Critical Limb Ischemia (CLI)　- A Joint USA-Japanese Perspective.

For more than 10 years, the Harmonization by Doing (HBD) program, a joint effort by members from academia, industry and regulators from the United States of America (USA) and Japan, has been working to increase timely regulatory approval for cardiovascular devices through the development of practical global clinical trial paradigms. Consistent with this mission and in recognition of the increasing global public health effects of critical limb ischemia (CLI), academic and government experts from the USA and Japan have developed a basic framework of global clinical trials for endovascular devices for CLI. Despite differences in medical and regulatory environments and complex patient populations in both countries, we developed a pathway for the effective design and conduct of global CLI device studies by utilizing common study design elements such as patients' characteristics and study endpoints, and minimizing the effect of important clinical differences. Some of the key recommendations for conducting global CLI device studies are: including patients on dialysis; using a composite primary endpoint for effectiveness that includes 6-month post-procedure therapeutic success and target vessel patency; and using a 30-day primary safety endpoint of perioperative death and major adverse limb events. The proposed approach will be uniquely beneficial in facilitating both the initiation and interpretation of CLI studies and accelerating worldwide CLI device development and innovation.

Percutaneous Endovascular Aortic Aneurysm Repair for Abdominal Aortic Aneurysm.

PURPOSE OF REVIEW: This review discusses the benefits of a completely percutaneous approach to endovascular aortic aneurysm repair (EVAR), and provides an outline as to how this is performed by a multidisciplinary team of cardiologists and cardiovascular surgeons at a quaternary care community hospital. RECENT FINDINGS: Percutaneous endovascular aortic aneurysm repair (PEVAR) as compared to EVAR utilizing surgical femoral artery exposure is associated with a significant reduction in operation time, length of stay, access site complications, patient discomfort, and procedural cost. Furthermore, PEVAR may be the preferred approach in patients presenting with aneurysm rupture, as the avoidance of general anesthesia has been associated with improved 30-day mortality. Assuming no contraindication based on vascular anatomy, clinical status, or patient preference, these findings suggest that in properly selected patients, PEVAR should be the primary method for abdominal aortic aneurysm repair in both stable and unstable patients.