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.

One-Year Outcomes Following Directional Atherectomy of Popliteal Artery Lesions: Subgroup Analysis of the Prospective, Multicenter DEFINITIVE LE Trial.

PURPOSE: To report the effectiveness of directional atherectomy for the treatment of popliteal artery occlusive disease. METHODS: This subset of the prospective, multicenter, single-arm DEFINITIVE LE trial included 158 patients (mean age 72.0±10.9 years; 82 men) who underwent directional atherectomy in 162 popliteal artery lesions between 2009 and 2011. Forty-eight (30.4%) patients were suffering from critical limb ischemia (CLI). The mean lesion length was 5.8±3.9 cm; 38 (23.5%) arteries were occluded. The primary outcome measure for patients with intermittent claudication (IC) was duplex ultrasound-defined primary patency at 1 year; the outcome for subjects with CLI was freedom from major amputation of the target limb at 1 year. Outcomes and adverse events were independently assessed. RESULTS: Procedure success (≤30% residual stenosis) was achieved in 84.4% of treated lesions; adjunctive stenting was required in 6 (3.7%) of the 162 lesions. The 1-year primary patency rate was 75.0% (IC patients 78.2% and CLI patients 67.5%, p=0.118). The freedom from major amputation in both cohorts was 100%. In both IC and CLI patients, significant improvements were demonstrated at 1 year in the Rutherford category, walking distance, and quality of life in comparison to baseline. CONCLUSION: This study indicates that directional atherectomy in popliteal arteries leads to favorable technical and clinical results at 1 year for claudicant as well as CLI patients.

Analysis of IN.PACT DEEP trial on the association between changes in perfusion from pre- to postrevascularization and clinical outcomes in critical limb ischemia.

OBJECTIVES: To quantify changes in ankle and toe pressure from pre- to post-endovascular revascularization for critical limb ischemia (CLI) and examine their association with major adverse limb events (MALE). BACKGROUND: Despite societal guidelines recommendation of routine hemodynamic surveillance following revascularization, little is known about hemodynamic assessment in CLI. METHODS: Among the 358 patients with CLI from the international multicenter IN.PACT DEEP trial, ankle and toe pressures measurements were available at both baseline and after intervention in 270 and 44 patients, respectively. The change in ankle and toe pressures in response to endovascular revascularization and its association with 1-year MALE (target limb revascularization, amputation, or death) were examined using Kaplan-Meier curves and multivariable Cox proportional hazard analyses. Corresponding optimal cutoff points were also identified. RESULTS: The mean increase in ankle and toe pressures following revascularization was 33 and 13 mmHg, respectively. Patients with an improvement of ankle pressure >73 mmHg or toe pressure >1 mmHg had similarly the lowest incidence of MALE (23%), while the highest rate of MALE (50%) was found in those whose toe pressure failed to improve by at least 1 mmHg following intervention. In addition, an increase in ankle pressure >73 mmHg was numerically protective against MALE, and more importantly, an increase in toe pressure of >1 mmHg provided statistically significant protection from MALE (adjusted HR = 0.15, 95% CI: 0.04-0.57, P = 0.005). CONCLUSIONS: Improvements in toe pressure post revascularization are incremental and rarely normalize. Toe pressure, compared to ankle pressure, is more useful in CLI and predicts future MALE.

Angiographic classification of patterns of restenosis following femoropopliteal artery intervention: A proposed scoring system.

OBJECTIVES: To propose a classification system for characterizing angiographic femoropopliteal artery restenosis patterns associated with common endovascular modalities. BACKGROUND: Peripheral artery disease is a worldwide issue affecting millions of people. Despite a myriad of endovascular technologies available to treat peripheral artery disease of the femoropopliteal arteries, restenosis remains a common failure mode. Characterizing common patterns of restenosis is important to discern the potential impact of baseline patient, lesion, and procedural characteristics, as well as treatment modalities on either the primary success or the failure patterns associated with restenosis. METHODS: Studies included in the analysis were from previous core laboratory-adjudicated femoropopliteal artery disease trials and registries reflecting a wide array of treatment modalities. RESULTS: From the subjects enrolled and analyzed, there were 403 total angiograms for analysis and adjudication. Target lesion revascularization images of the 32 validation cases were evaluated for index treated length, diameter stenosis, and lesion morphology characteristics. The following lesion types are proposed: Type 1 "Focal" pattern, which may be "Edge Proximal" or "Edge Distal" depending on location; a Type 2 "Multifocal" pattern which may also exhibit edge restenosis, but may also be "Edge Bilateral"; a Type 3 "Moderate" pattern and a Type 4 "Diffuse" pattern; and finally, a Type 5 "Occlusion". CONCLUSIONS: A classification system that enables healthcare professionals to anticipate and describe failures following the index procedure, thereby impacting the choice of options for retreatment, may facilitate consistency and standardization within the heterogeneous field of endovascular device treatments for the femoropopliteal artery.

Patient-level meta-analysis of 999 claudicants undergoing primary femoropopliteal nitinol stent implantation.

CONDENSED ABSTRACT: The factors that impact the clinical effectiveness of bare nitinol stents in claudicants with symptomatic femoropopliteal atherosclerosis are incompletely known. The authors analyzed variables that may influence stent durability and provide a benchmark for their effectiveness. Data analyzed from six studies (999 patients) included baseline noninvasive hemodynamic tests, angiographic characteristics, ultrasound defined stent patency and target lesion revascularization through 12-months. Baseline ankle-brachial index and lesion length predicted stent patency and target lesion revascularization and when combined interacted significantly to better predict outcomes. This meta-analysis provides an important comparator against which emerging therapies that treat claudicants with femoropopliteal atherosclerosis can be assessed. SUBJECT CODE: Peripheral Artery Disease BACKGROUND: The performance of bare metal nitinol stents in patients with symptomatic femoropopliteal peripheral artery disease (PAD) is not well defined. METHODS: Patient-level data from six large prospective trials sponsored by medical device manufacturers was abstracted and analyzed to identify a cohort of patients with claudication and femoropopliteal artery occlusive disease. Twelve-month binary patency and target lesion revascularization (TLR) rates were primary outcomes. Stent patency was assessed by duplex ultrasonography (DUS) and TLR was a clinically driven intervention. To characterize the effects of patient characteristics on the outcomes, meta-regression was performed via mixed effects logistic regression models with patient-level covariates. RESULTS: About 999 patients were analyzed; the mean ABI was 0.68 ± 0.18, the mean lesion length was 84 ± 53 mm, the mean lesion stenosis was 78%, and nearly two thirds of patients had mild to severe calcification. The mean Rutherford clinical category was 2.7 ± 0.6 and ranged from 2.6 to 2.8 in all studies. The 12-month patency across all studies was 69.8% and TLR rates ranged from 9.2% to 19.7%. Multivariable analysis demonstrated that baseline ABI and baseline target lesion length predicted both primary patency and TLR. Further, these two variables interacted significantly to better predict TLR outcomes when used in combination. CONCLUSION: The 12-month clinical effectiveness of bare nitinol stents to treat patients with symptomatic femoropopliteal PAD is acceptable and is impacted by clinical and lesion-specific characteristics. These data provide an important and useful benchmark to compare the clinical benefit of emerging endovascular PAD therapies. © 2017 Wiley Periodicals, Inc.

An analysis of IN.PACT DEEP randomized trial on the limitations of the societal guidelines-recommended hemodynamic parameters to diagnose critical limb ischemia.

OBJECTIVE: Recent small single-center data indicate that the current hemodynamic parameters used to diagnose critical limb ischemia are insensitive. We investigated the validity of the societal guidelines-recommended hemodynamic parameters against core laboratory-adjudicated angiographic data from the multicenter IN.PACT DEEP (RandomIzed AmPhirion DEEP DEB vs StAndard PTA for the treatment of below the knee Critical limb ischemia) Trial. METHODS: Of the 358 patients in the IN.PACT DEEP Trial to assess drug-eluting balloon vs standard balloon angioplasty for infrapopliteal disease, 237 had isolated infrapopliteal disease with an available ankle-brachial index (ABI), and only 40 of the latter had available toe pressure measurements. The associations between ABI, ankle pressure, and toe pressure with tibial runoff, Rutherford category, and plantar arch were examined according to the cutoff points recommended by the societal guidelines. Abnormal tibial runoff was defined as severely stenotic (≥70%) or occluded and scored as one-, two-, or three-vessel disease. A stenotic or occluded plantar arch was considered abnormal. RESULTS: Only 14 of 237 patients (6%) had an ABI <0.4. Abnormal ankle pressure, defined as <50 mm Hg if Rutherford category 4 and <70 mm Hg if Rutherford category 5 or 6, was found only in 37 patients (16%). Abnormal toe pressure, defined as <30 mm Hg if Rutherford category 4 and <50 mm Hg if Rutherford category 5 or 6, was found in 24 of 40 patients (60%) with available measurements. Importantly, 29% of these 24 patients had an ABI within normal reference ranges. A univariate multinomial logistic regression found no association between the above hemodynamic parameters and the number of diseased infrapopliteal vessels. However, there was a significant paradoxic association where patients with Rutherford category 6 had higher ABI and ankle pressure than those with Rutherford category 5. Similarly, there was no association between ABI and pedal arch patency. CONCLUSIONS: The current recommended hemodynamic parameters fail to identify a significant portion of patients with lower extremity ulcers and angiographically proven severe disease. Toe pressure has better sensitivity and should be considered in all patients with critical limb ischemia.

A single stent strategy in patients with lifestyle limiting claudication: 3-year results from the Durability II trial.

OBJECTIVES: To evaluate longer-term safety and efficacy of a single self-expanding stent up to 20 cm in length in patients with atherosclerotic disease of the superficial femoral (SFA) and proximal popliteal arteries. BACKGROUND: Angioplasty and stenting are options for revascularization of symptomatic peripheral artery disease. While angioplasty alone is effective in short lesions, outcomes in longer lesions (i.e., mean 8.7 cm) show suboptimal patency rates of 33% at one year. METHODS: Two hundred eighty-seven patients (mean age 68 years, 66% male) were treated with the EverFlex™ Self-Expanding Peripheral Stent System. Patients were followed through 3 years with yearly core lab adjudicated duplex ultrasonography for patency, radiographic assessment of stent fractures, and resting ankle brachial indices. RESULTS: Overall freedom from loss of primary patency at 3 years was 60.0%. Patency was significantly higher for lesions ≤8 cm compared with lesions >8 cm (71.0 vs. 50.5%, P < 0.0001). There was no significant difference in patency between single-stent and multistent recipients (60.4 vs. 52.4%, P = 0.343). The three-year freedom from clinically driven target lesion revascularization was 70.0%. At 3 years, the overall stent fracture rate was 0.9%. CONCLUSIONS: DURABILITY II is the first investigational device exemption trial to report 3-year duplex Doppler defined stent patency and CD-TLR outcomes in long SFA and proximal popliteal lesions and demonstrated acceptable stent patency and freedom from CD-TLR with a low fracture rate. These data suggest that use of a single long stent provides reasonable long-term outcomes when intervention is required for symptomatic SFA and proximal popliteal arterial disease.

The ROX coupler: creation of a fixed iliac arteriovenous anastomosis for the treatment of uncontrolled systemic arterial hypertension, exploiting the physical properties of the arterial vasculature.

OBJECTIVES: Uncontrolled hypertension, whether due to drug resistance or poor adherence and persistence, remains a problem in many patients. The ROX coupler is a novel technology designed to reduce arterial blood pressure consequent to the predicted physical effects of reducing vascular resistance and improving arterial compliance. This article describes the technical aspects of the device and implantation procedure, results from a preclinical study, patient selection criteria, and potential complications of this therapy for uncontrolled hypertension. BACKGROUND: The coupler is a self-expanding, stent-like device that exploits the mechanical effects of the creation of a low-resistance, high-compliance venous segment to the central arterial tree, and can be implanted in a standard catheterization laboratory under fluoroscopic guidance. METHODS: Preclinical studies were conducted in sheep with acute or chronic hypertension. The devices were implanted in the aorta for up to 12 months. The anastomoses were evaluated for patency, healing, conformation into the artery and vein, and complications. RESULTS: Deployment of the anastomotic device in ovine aortas for up to 12 months showed optimal anastomotic patency in all animals with proper healing and conformation of the device into the artery and the vein. There was no significant residual mural thrombus and minimal to moderate intimal thickening at the vein outflow, consistent with expected arterialization. CONCLUSIONS: A novel arteriovenous coupler for percutaneous placement in the iliac vasculature is under clinical investigation as a potential treatment modality for selected patients with uncontrolled hypertension. Initial results from patients with uncontrolled hypertension are expected in Autumn 2014.

One-Year Outcomes Following Directional Atherectomy of Infrapopliteal Artery Lesions: Subgroup Results of the Prospective, Multicenter DEFINITIVE LE Trial.

PURPOSE: To report a subgroup analysis of the prospective, multicenter, single-arm DEFINITIVE LE trial to assess the effectiveness of directional atherectomy for the treatment of infrapopliteal artery lesions at 1 year. METHODS: In the DEFINITIVE LE trial, follow-up assessments occurred up to 1 year postprocedure. Of the 800 patients enrolled, 145 subjects with 189 infrapopliteal lesions met the criteria for this analysis. Seventy (48.3%) and 75 (51.7%) patients were suffering critical limb ischemia (CLI) and intermittent claudication, respectively; 68.3% (99/145) had diabetes. The mean lesion length was 58±44 mm (all lesions); 20.2% were occluded. The primary endpoint for patients with claudication was duplex ultrasound-derived primary patency, while for subjects with CLI it was freedom from major amputation of the target limb at 1 year. Endpoints and adverse events were independently assessed. RESULTS: Procedure success (≤30% residual stenosis) was achieved in 84% of treated lesions. The 1-year primary patency rate was 84% (claudicants 89.6% and CLI patients 78%, p=0.11), and the freedom from major amputation rate was 97.1% (claudicants 100% and CLI 93.8%, p=0.03). In both claudication and CLI patients, significant improvements in Rutherford category and objective measures of walking distance and quality of life were seen at 1 year in comparison to baseline. CONCLUSION: This study demonstrates that directional atherectomy in infrapopliteal arteries results in promising technical and clinical results at 1 year for claudicant as well as CLI patients.

A Comparison of Clinical Outcomes for Diabetic and Nondiabetic Patients Following Directional Atherectomy in the DEFINITIVE LE Claudicant Cohort.

PURPOSE: To report a subset analysis that evaluated the hypothesis that directional atherectomy for peripheral artery disease in diabetic claudicants has noninferior primary patency at 12 months compared with nondiabetic claudicants. METHODS: DEFINITIVE LE, a US/European multicenter study, assessed the effectiveness of directional atherectomy using SilverHawk/TurboHawk systems for treatment of peripheral artery disease in the superficial femoral, popliteal, and infrapopliteal arteries. Of the 800 patients enrolled in the study, only the 598 claudicant patients (mean age 69.5±10.4 years; 336 men) who were classified at baseline as Rutherford category 1-3 were eligible for this subset analysis. Of these, 46.8% (280/598) had diabetes. Follow-up to 12 months included duplex ultrasound examination, functional assessments, and adverse event evaluations. Independent angiographic and duplex ultrasound core laboratories assessed primary patency and secondary endpoints; a clinical events committee adjudicated adverse events. RESULTS: Although diabetics had significantly more baseline comorbidities, 12-month primary patency (77.0%) was no different than for nondiabetics (77.9%; superiority p=0.98; noninferiority p<0.001) across all anatomic territories treated. Freedom from clinically driven target lesion revascularization was no different between diabetics (83.8%) and nondiabetics (87.5%) overall (p=0.19) or by lesion locations. Secondary clinical outcomes (Rutherford category, ankle-brachial index, and walking impairment) improved at 12 months for both diabetics and nondiabetics. CONCLUSION: Noninferior 12-month patency rates demonstrate that directional atherectomy is an effective treatment in diabetic as well as nondiabetic claudicants. Directional atherectomy remains an attractive treatment option, improving luminal diameters without stents, which preserves future treatment options for both diabetic and nondiabetic patients with progressive, diffuse vascular disease.

Proceedings from Duke resistant hypertension think tank.

To identify patients at increased risk for cardiovascular outcomes, apparent treatment resistant hypertension (aTRH) is defined as having a blood pressure (BP) above goal despite the use of ≥3 antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. In light of growing scientific interest in the treatment of this group, a multistakeholder think tank was convened to discuss the current state of knowledge, improve the care of these patients, and identify appropriate study populations for future observational and randomized trials in the field. Although recent epidemiologic studies in selected populations estimate that the prevalence of aTRH is 10% to 15% of hypertensive patients, further large-scale observational studies will be needed to better elucidate risk factors. To spur the development of therapies for aTRH, the development of an "aTRH" label for pharmacologic and device therapies with a developmental pathway including treatment added to the use of existing therapies is favored. Although demonstration of adequate BP lowering should be sufficient to gain Food and Drug Administration approval for therapies targeting aTRH, assessment of improvement in quality of life and cardiovascular outcomes is also desirable and considered in Centers for Medicare and Medicaid Services coverage decisions. Device trials under the aTRH label will need uniform and consistent processes for defining appropriate patient populations as well as postapproval registries assessing both long-term safety and duration of responses. Finally, patients with aTRH are likely to benefit from evaluation by a hypertension team to assure proper patient identification, diagnostic work-up, and therapeutic management before consideration of advanced or novel therapies to lower BP.

Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications.

Vascular calcification (VC), particularly medial (Mönckeberg's medial sclerosis) arterial calcification, is common in patients with diabetes mellitus and chronic kidney disease and is associated with increased cardiovascular morbidity and mortality. Although, the underlying pathophysiological mechanisms and genetic pathways of VC are not fully known, hypocalcemia, hyperphosphatemia, and the suppression of parathyroid hormone activity are central to the development of vessel mineralization and, consequently, bone demineralization. In addition to preventive measures, such as the modification of atherosclerotic cardiovascular risk factors, current treatment strategies include the use of calcium-free phosphate binders, vitamin D analogs, and calcium mimetics that have shown promising results, albeit in small patient cohorts. The impact of intimal and medial VC on the safety and effectiveness of endovascular devices to treat symptomatic peripheral arterial disease (PAD) remains poorly defined. The absence of a generally accepted, validated vascular calcium grading scale hampers clinical progress in assessing the safety and utility of various endovascular devices (e.g., atherectomy) in treating calcified vessels. Accordingly, we propose the peripheral arterial calcium scoring system (PACSS) and a method for its clinical validation. A better understanding of the pathogenesis of vascular calcification and the development of optimal medical and endovascular treatment strategies are crucial as the population ages and presents with more chronic comorbidities.

The impact of sex on angioplasty and primary stenting for femoropopliteal occlusive disease: results of the DURABILITY II trial.

BACKGROUND: This study investigates the impact of sex on angioplasty and primary stenting for the treatment of claudicants with femoropopliteal occlusive disease (FPOD). METHODS: Two hundred eighty-seven patients enrolled in the Safety and Effectiveness Study of EverFlex Stent to Treat Symptomatic Femoral-popliteal Atherosclerosis (DURABILITY II) trial (a prospective, nonrandomized, core laboratory audited, and independently adjudicated investigational device exemption trial) were stratified by sex (190 men and 97 women) and reviewed. RESULTS: Women presented with FPOD at an older age than men (71.3 ± 11.2 vs. 65.9 ± 9.9 years; P < 0.001). Men were more likely to be hyperlipidemic (89.5% vs. 79.4%; P = 0.030). No other statistically significant differences were observed with regard to periprocedural comorbidities and demographics. Clinically, women presented more often with severe claudication (64.9% vs. 51.1%; P = 0.033) as compared with men that had more moderate claudication (44.2% vs. 29.9%; P = 0.022). The incidence of rest pain and tissue loss was low and did not vary between sexes. Angiographically, women had smaller reference vessels (4.4 ± 0.8 mm vs. 5.0 ± 0.9 mm; P < 0.001). Longer lesions (91.6 ± 46.8 mm vs. 87.8 ± 43.9 mm) and higher primary (79.0% vs. 76.5%), primary-assisted (90.6% vs. 85.1%), and secondary patency (90.6% vs. 85.7%) rates in women did not achieve statistical significance (P = NS). Mean percent stenosis and occlusion rates were similar between groups, but men were more likely to have severe calcification (47.9% vs. 34.0%; P = 0.020). Inter-Society Consensus for the Management of Peripheral Arterial Disease II classifications were similar between groups. The target lesion revascularization, major adverse event, and mortality rates were similar between groups. At baseline, the absolute claudication distance was 0.29 miles for men, while women only reached 0.14 miles (P < 0.0001). Walking improvement questionnaire scores were also compared; women had significantly lower scores at baseline and at 1 year. CONCLUSIONS: Despite presenting with FPOD at a later age, with more severe claudication, a shorter absolute claudication distance, and smaller vessels than men, women achieved equal patency rates using angioplasty and primary stenting with similar target lesion revascularization, major adverse event, and mortality rates. Despite these findings, women subjectively have worse symptoms at baseline and at 1 year.

Five-Year Safety and Effectiveness of Paclitaxel Drug-Coated Balloons Alone or With Provisional Bare Metal Stenting for Real-World Femoropopliteal Lesions: IN.PACT Global Study Subgroup Analysis.

BACKGROUND: The treatment of complex infra-inguinal disease with drug-coated balloons (DCBs) is associated with a significant number of patients undergoing provisional stenting to treat a suboptimal result. To determine the potential long-term impact of DCB treatment with provisional bare metal stenting in complex lesions in real-world patients, a post hoc analysis was performed on data from the IN.PACT Global Study (The IN.PACT Global Clinical Study for the Treatment of Comprehensive Superficial Femoral and/or Popliteal Artery Lesions Using the IN.PACT Admiral Drug-Eluting Balloon). Five-year outcomes were compared between participants who were stented after DCB treatment versus those treated with DCB alone. METHODS: The IN.PACT Global Study enrolled 1535 participants with intermittent claudication and/or ischemic rest pain caused by femoropopliteal lesions; 1397 patients were included in this subgroup analysis (353 stented and 1044 nonstented). Effectiveness was assessed as freedom from clinically driven target lesion revascularization through 60 months. The primary safety composite end point was defined as freedom from device- and procedure-related death through 30 days, and freedom from major target limb amputation and clinically driven target vessel revascularization through 60 months. RESULTS: Lesions in the stented group were longer (15.37 versus 10.98 cm; P<0.001) and had more total occlusions (54.7% versus 28.6%; P<0.001) compared with the nonstented group. The 5-year Kaplan-Meier estimated freedom from clinically driven target lesion revascularization was similar between groups (66.8% stented versus 70.0% nonstented group, log-rank P=0.22). The safety composite end point was achieved in 64.5% stented versus 68.2% nonstented participants (log-rank P=0.19) as estimated by the Kaplan-Meier method. No significant difference was observed in the cumulative incidence of major adverse events (49.1% stented versus 45.0% nonstented; log-rank P=0.17), including all-cause death (19.6% stented versus 19.3% nonstented, log-rank P=0.99). CONCLUSIONS: In this real-world study, revascularization of complex femoropopliteal artery lesions with DCB angioplasty alone or DCB followed by provisional bare metal stenting in certain lesions achieved comparable long-term safety and clinical effectiveness. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609296.

The United States StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol STent SYstem II (DURABILITY II).

OBJECTIVE: Angioplasty and stenting are options for revascularization of symptomatic femoral popliteal disease. Although angioplasty alone is effective in short lesions, longer lesions are often treated with stents. Multiple overlapping stents are expensive and may be associated with stent fracture. This trial evaluated the safety and efficacy of a single self-expanding stent up to 20 cm in length in patients with atherosclerotic disease of the superficial femoral artery (SFA) and proximal popliteal artery. METHODS: Patients with lesions >4 cm and <18 cm were enrolled in this nonrandomized, prospective, multicenter trial that evaluated the Protégé EverFlex Self-Expanding Peripheral Stent System (Covidien, Plymouth, Minn). The study's primary end points were the 30-day major adverse event rate and duplex ultrasound-assessed patency at 1 year. These were compared with published performance goals. A preplanned analysis was conducted for the primary effectiveness end points at 1 year. Follow-up, including history, ankle-brachial index, patient-reported outcomes, duplex ultrasound assessment, and radiographs, is planned through 3 years. There was core laboratory review of angiograms, ultrasound scans, and plain radiographs. A subgroup of patients was studied with graded treadmill testing. RESULTS: The study enrolled 287 patients (66% male; mean age, 68 years) with stenotic, restenotic, or occluded lesions of the SFA at 44 investigational sites in the United States and Europe. Systemic comorbidities included hypertension (88%), hyperlipidemia (86%), diabetes (43%), and prior SFA intervention (41%). The mean lesion length measured by the core laboratory was 89 mm. The mean normal-to-normal lesion length measured by sites was 110 mm. A total of 303 stents were implanted, and 95% of patients received a single stent. No major adverse events occurred at 30 days. At 1 year, primary outcome of duplex ultrasound stent patency was 67.7% in evaluable patients, and among 1-year secondary outcomes, the mean ankle-brachial index increased by 0.25. Walking Improvement Questionnaire scores improved in pain by 33.7, distance by 37.1, speed by 18.6, and stair climbing by 24.7. The Kaplan-Meier estimate of primary patency was 77.2%, primary assisted patency was 86.9%, and secondary patency was 87.3%. Rutherford clinical category improved in 83.5% of patients. Stent fracture rate was 0.4%. Matched absolute claudication distance was 412 feet greater and was not statistically different in this subgroup of 29 individuals. CONCLUSIONS: The results of DURABILITY II (StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol Stent SYstem II) suggest that a new single stent strategy is safe and effective for the treatment of long lesions of the SFA and proximal popliteal arteries at 1 year.

Comparison of Drug-Coated Balloons vs Bare-Metal Stents in Patients With Femoropopliteal Arterial Disease.

BACKGROUND: Endovascular treatment of femoropopliteal artery disease has shifted toward drug-coated balloons (DCB). However, limited data are available regarding the safety and efficacy of DCB vs bare-metal stents (BMS). OBJECTIVES: The purpose of this study was to compare DCB vs BMS outcomes in a propensity-adjusted, pooled analysis of 4 prospective, multicenter trials. METHODS: Patient-level data were pooled from 4 prospective, multicenter studies: the IN.PACT SFA I/II and IN.PACT SFA Japan randomized controlled DCB trials and the Complete SE and DURABILITY II single-arm BMS studies. Outcomes were compared using inverse probability of treatment weighting (IPTW). Clinical endpoints were 12-month primary patency, freedom from 36-month clinically driven target lesion revascularization, and cumulative 36-month major adverse events (MAE). RESULTS: The primary analysis included 771 patients (288 DCB, 483 BMS). IPTW-adjusted demographic, baseline lesion, and procedural characteristics were matched between groups. The adjusted mean lesion length was 8.1 ± 4.7 cm DCB and 7.9 ± 4.5 cm BMS. The IPTW-adjusted Kaplan-Meier estimates of 12-month primary patency (90.4% DCB, 80.9% BMS, P = 0.007), freedom from 36-month clinically driven target lesion revascularization (85.6% DCB, 73.7% BMS, P = 0.001), and cumulative incidence of 36-month MAE (25.3% DCB, 38.8% BMS, P < 0.001) favored DCB. There were no statistically significant differences observed in all-cause mortality, target limb major amputation, or thrombosis through 36 months. CONCLUSIONS: In a patient-level, IPTW-adjusted pooled analysis of prospective, multicenter pivotal studies, DCB demonstrated significantly higher patency, lower revascularization and MAE rates, and no statistically significant differences in mortality, amputation, or thrombosis vs BMS. This analysis supports DCB use vs BMS in moderately complex femoropopliteal lesions amenable to both treatments.

Major adverse limb events and wound healing following infrapopliteal artery stent implantation in patients with critical limb ischemia: the XCELL trial.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) with stent deployment of infrapopliteal arteries is an accepted but unproven therapy for patients with critical limb ischemia (CLI). We evaluated the safety and effectiveness of the Xpert™ self-expanding nitinol stent (Abbott Vascular, Redwood City, CA) in Rutherford Class 4-6 subjects with infrapopliteal lesions of 4-15 cm in length. METHODS AND RESULTS: 120 patients (140 limbs, 212 implanted devices) underwent primary infrapopliteal nitinol stent deployment as part of this multicenter registry. The primary endpoint was 12-month amputation-free survival (AFS); secondary endpoints included limb salvage, target lesion revascularization (TLR), 6- month angiographic patency, and 6- and 12-month outcomes of wound healing and pain relief. Despite a 6-month binary stent restenosis rate of 68.5%, the 12-month AFS rate was 78.3%. Stratified according to baseline Rutherford classes 4, 5 and 6, the 12-month AFS rates were 100%, 77.3%, and 55.2%, respectively, and freedom from major amputation rates were 100%, 90.9%, and 70.1%, respectively. The 12-month freedom from major amputation rate and clinically driven TLR were 89.6% and 70.1%, respectively. The 6- and 12-month complete wound-healing rates were 49.0% and 54.4%, respectively. Rutherford class 4 patients had significant pain relief through 12-months (P<0.05). CONCLUSIONS: Primary infrapopliteal nitinol stenting to treat CLI is safe and effective in improving 6-and 12-month clinical outcomes.

Endovascular therapy for vasculogenic erectile dysfunction.

OPINION STATEMENT: Erectile dysfunction (ED) is an important clinical condition that affects a significant proportion of men. Although there are many etiologies for ED, many cases have a vascular basis that is related to inadequate arterial inflow, veno-occlusive dysfunction, or abnormalities in smooth muscle (cavernosal tissue) relaxation. These vascular abnormalities can exist in isolation or combination. Since the advent of phosphodiesterase-5 inhibitor (PDE5i) therapy, the initial management of ED in most cases consists of a brief medical evaluation followed by a trial of PDE5i therapy. However, up to 50% of men have an inadequate response to PDE5i therapy and discontinue therapy. Subsequent therapies for ED are increasingly invasive, including penile injection of vasodilators, vacuum pumps, and penile implants. With increased awareness of ED among clinicians and the growing mechanistic link between ED and atherosclerotic vascular disease, there has been renewed interest in the diagnosis and management of arteriogenic ED. Prior reports in the 1980s described the existence of arterial inflow lesions in patients with ED, and there are a modest number of reports describing the feasibility of revascularization with balloon angioplasty. Despite initial clinical success, enthusiasm for this technique waned, presumably because ED frequently recurred due to restenosis and lack of small vessel endovascular therapies. Recent investigation and the availability of newer tools such as drug-eluting stents have renewed interest in this field. Although conceptually attractive, endovascular therapy for ED presents significant challenges related to unanswered questions such as the prevalence and appropriate diagnostic evaluation of arteriogenic ED, and the safety and feasibility of stent-based therapies in this population. In addition, the evaluation, management, and follow-up of patients with vascular ED require a multi-disciplinary team with specialists in urology, sexual medicine, and vascular medicine. Despite these challenges, the potential for endovascular treatment of these patients remains one of the most exciting areas of investigation in vascular medicine.

Objective performance goals of safety and blood pressure efficacy for clinical trials of renal artery bare metal stents in hypertensive patients with atherosclerotic renal artery stenosis.

OBJECTIVE: To provide safety and performance goals for prospective single-arm trials of bare metal renal artery stenting in patients with resistant hypertension associated with high grade atherosclerotic renal artery stenosis. BACKGROUND: To date, there have been no US Pre-Market Approval (PMA) bare metal renal stent device trials which have focused on improvement of blood pressure control as a primary effectiveness endpoint. METHODS: Analysis of subject-level data from three large industry sponsored pre-market approval (PMA) trials was performed. Hypertensive patients (≥ 155 mmHg) with a ≥ 50% atherosclerotic renal artery stenosis were included. Thirty day and 9-month systolic and diastolic blood pressure measurements, renal function and 9-month duplex ultrasound assessment of renal artery patency were analyzed. RESULTS: Initial data analysis of 600 patients from the 3 PMA trials identified 286 patients who met inclusion criteria. The mean baseline systolic blood pressure was 177.8 ± 19.3 mmHg with a mean 68.1% diameter renal artery stenosis. Nine months after successful stenting, the mean SBP was 156.7 ± 24.1 mmHg; the 9 month restenosis rate was 14.4%. CONCLUSION: Based on the statistical modeling of these data and a priori established performance criteria, the co-primary endpoints of 9 month reduction in blood pressure and in-stent restenosis are proposed. The reduction in blood pressure will be analyzed as a continuous variable and will be compared to this performance goal.