Methods, design, and initial results of an angiographic core lab from VOYAGER-PAD.

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216).

Efficacy and safety of rivaroxaban versus placebo after lower extremity bypass surgery: A post hoc analysis of a "CASPAR like" outcome from VOYAGER PAD.

BACKGROUND: The Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease (CASPAR) trial is the only large, double-blind, placebo-controlled trial of dual antiplatelet therapy (DAPT) versus aspirin in patients with peripheral artery disease (PAD) after lower extremity revascularization (LER). The trial was neutral for index-graft occlusion/revascularization, amputation or death (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.78-1.23, p = .87) with an excess of global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries moderate or severe bleeding (HR 2.84, 95% CI 1.32-6.08, p = .007). HYPOTHESIS AND METHODS: VOYAGER-PAD demonstrated that rivaroxaban significantly reduces acute limb ischemia (ALI), major amputation, myocardial infarction (MI), stroke and CV death but increased bleeding. The relative efficacy and safety of rivaroxaban in a CASPAR like population and for similar outcomes is unknown. The current analysis is a post-hoc exploratory analysis of a "CASPAR like" composite of ALI, unplanned index limb revascularization (UILR), amputation or CV death in surgical patients. RESULTS: In the 2185 who underwent surgical LER, rivaroxaban reduced the CASPAR endpoint at 1 (HR 0.76, 95% CI 0.62-0.95, p = .0133) and 3 years (HR 0.84, 95% CI 0.71-1.00, p = .0461, Figure). There were similar reductions in composites of ALI, amputation or CV death (HR 0.79, p = .0228) and ALI, UILR, amputation, MI, IS or CV death (HR 0.85, p = .0410). CONCLUSIONS: The combination of rivaroxaban and aspirin significantly reduces ischemic outcomes in patients with PAD after LER. Although no formal head-to-head comparison exists, in a similar population and for similar outcomes, this regimen demonstrated benefit where trials of DAPT were neutral. These data suggest that factor Xa inhibition may provide specific benefits in this population and that DAPT should not be considered a proven substitution.

In vivo evaluation of a new hybrid graft using retrograde visceral perfusion for thoracoabdominal aortic repair in an animal model.

Objectives: The SPIDER technique for hybrid thoracoabdominal aortic aneurysm repair can avoid thoracotomy and extracorporeal circulation. To improve technical feasibility and safety, the new Thoracoflo graft, consisting of a proximal stent graft connected to a 7-branched abdominal prosthesis, was evaluated in a pig model for technical feasibility testing, before implantation in humans. Methods: Retroperitoneal exposure of the infradiaphragmatic aorta, including visceral and renal arteries, was performed in 7 pigs (75-85 kg). One iliac branch was temporarily attached to the distal aorta to maintain retrograde visceral and antegrade iliac perfusion after deployment of the thoracic stent graft segment (SPIDER technique). The proximal stent-grafted segment was deployed in the thoracic aorta via direct aortic puncture over the wire without fluoroscopy. The graft was deaired before flow via the iliac side branch to the visceral and iliac arteries was established. Visceral, renal, and lumbar arteries were subsequently sutured to the corresponding side branches of the graft. Technical feasibility, operating and clamping time, blood flow, and tissue perfusion in the related organs were evaluated before implantation and after 3 and 6 hours using transit-time flow measurement and fluorescent microspheres. Final angiography or postprocedural computed tomography angiography were performed. Results: Over-the-wire graft deployment was successful in 6 animals without hemodynamic alteration (P = n.s.). In 1 pig, the proximal stent graft section migrated as the guidewire was not removed, as recommended, before release of the proximal fixation wire. Angiography and computed tomography scan confirmed successful graft implantation and transit-time flow measurement confirmed good visceral and iliac blood flow. Fluorescent microspheres confirmed good spinal cord perfusion. Conclusions: Over-the-wire implantation of the Thoracoflo graft using the SPIDER technique is feasible in a pig model. No fluoroscopy was required. For safe implantation, it is mandatory to follow the single steps of implantation.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. METHODS: SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. FINDINGS: 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. INTERPRETATION: CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. FUNDING: German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Pulsed low-intensity laser treatment stimulates wound healing without enhancing biofilm development in vitro.

OBJECTIVES: Treating infected or chronic wounds burdened with biofilms still is a major challenge in medical care. Healing-stimulating factors lose their efficacy due to bacterial degradation, and antimicrobial substances negatively affect dermal cells. Therefore, alternative treatment approaches like the pulsed low intensity laser therapy (LILT) require consideration. METHODS: The effect of pulsed LILT (904 nm, in three frequencies) on relevant human cells of the wound healing process (fibroblasts (BJ), keratinocytes (HaCaT), endothelial cells (HMEC), monocytes (THP-1)) were investigated in in-vitro and ex-vivo wound models with respect to viability, proliferation and migration. Antimicrobial efficacy of the most efficient frequency in cell biological analyses of LILT (3200 Hz) was determined in a human biofilm model (lhBIOM). Quantification of bacterial load was evaluated by suspension method and qualitative visualization was performed by scanning electron microscopy (SEM). RESULTS: Pulsed LILT at 904 nm at 3200 Hz ± 50% showed the most positive effects on metabolic activity and proliferation of human wound cells in vitro (after 72 h - BJ: BPT 0.97 ± 0.05 vs. 0.75 ± 0.04 (p = 0.0283); HaCaT: BPT 0.79 ± 0.04 vs. 0.59 ± 0.02 (p = 0.0106); HMEC: 0.74 ± 0.02 vs. 0.52 ± 0.04 (p = 0.009); THP-1: 0.58 ± 0.01 vs. 0.64 ± 0.01 (p > 0.05) and ex vivo. Interestingly, re-epithelialization was stimulated in a frequency-independent manner. The inhibition of metabolic activity after TNF-α application was abolished after laser treatment. No impact of LILT on monocytes was detected. Likewise, the tested LILT regimens showed no growth rate reducing effects on three bacterial strains (after 72 h - PA: -1.03%; SA: -0.02%; EF: -1,89%) and one fungal (-2.06%) biofilm producing species compared to the respective untreated control. Accordingly, no significant morphological changes of the biofilms were observed after LILT treatment in the SEM. CONCLUSIONS: Frequent application of LILT (904 nm, 3200 Hz) seems to be beneficial for the metabolism of human dermal cells during wound healing. Considering this, the lack of disturbance of the behavior of the immune cells and no growth-inducing effect on bacteria and fungi in the biofilm can be assigned as rather positive. Based on this combined mode of action, LILT may be an option for hard to heal wounds infected with persistent biofilms.

Sex-Based Differences in Outcomes Following Peripheral Artery Revascularization: Insights From VOYAGER PAD.

Background Despite high female prevalence of peripheral artery disease (PAD), little is known about sex-based outcomes after lower extremity revascularization (LER) for symptomatic PAD. The effects of rivaroxaban according to sex following LER have not been fully reported. Methods and Results In VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), low-dose rivaroxaban versus placebo on a background of aspirin reduced the composite primary efficacy outcome of cardiovascular and limb events in patients with PAD undergoing LER. Unplanned index limb revascularization was prespecified and prospectively ascertained. The primary safety outcome was Thrombolysis in Myocardial Infarction major bleeding. Analyses of outcomes and treatment effects by sex were performed using Cox proportional hazards models. Among 6564 randomly assigned patients followed for a median of 28 months, 1704 (26.0%) were women. Among patients administered placebo, women were at similar risk for the primary efficacy outcome (hazard ratio [HR], 0.90; [95% CI, 0.74-1.09]; P=0.29) as men, while female sex was associated with a trend toward higher risk of unplanned index limb revascularization (HR, 1.18; [95% CI, 1.00-1.40]; P=0.0499). Irrespective of sex, effects of rivaroxaban were consistent for the primary efficacy outcome (P-interaction=0.22), unplanned index limb revascularization (P-interaction=0.64), and bleeding (P-interaction=0.61). Women were more likely than men to discontinue study treatment (HR, 1.13; [95% CI, 1.03-1.25]; P=0.0099). Conclusions Among >1700 women with PAD undergoing LER, women and men were at similar risk for the primary outcome, but a trend for greater risk of unplanned index limb revascularization among women was observed. Effects of rivaroxaban were consistent by sex, though women more often discontinued treatment. Better understanding of sex-based outcomes and treatment adherence following LER is needed. Registration URL: http://clinicaltrials.gov; Unique identifier: NCT02504216.

Rivaroxaban and Risk of Venous Thromboembolism in Patients With Symptomatic Peripheral Artery Disease After Lower Extremity Revascularization.

Importance: Prior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER). Objective: To describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER. Design, Setting, and Participants: This global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021. Exposure: Randomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician. Main Outcomes and Measures: Symptomatic VTE was a prespecified secondary outcome and prospectively collected. Results: Among 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67). Conclusions and Relevance: In this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.

A cross-sectional survey study on the nutrition patterns of patients with peripheral artery disease.

Background: Even though nutrition was demonstrated to have an impact on chronic atherosclerotic disease, there is a paucity of corresponding recommendations for patients with peripheral artery disease (PAD). A Mediterranean Diet based on daily intake of fruits and vegetables with high fibre, vegetable oil, and unsalted nuts including fish several times a week may have protective effects. This cross-sectional survey aimed to determine nutritional patterns amongst inpatients with PAD. Methods: All inpatients with symptomatic PAD who underwent revascularisation at a single centre between 1st May 2018 and 31st December 2021 were asked to fill out a questionnaire on nutritional intake. An 8-item frequency rating scale (from never to three times a day) was used for 15 food groups. For 11 of them, an adapted Mediterranean Diet score was calculated using the answers. The descriptive results were stratified by sex and disease stage (intermittent claudication vs. chronic limb-threatening ischaemia). Results: A total of 319 patients (31.7% female, 69.4 years in mean) were included. Thereof, 71.8% reported they did never receive any nutritional information considering their PAD disease. The mean adapted Mediterranean Diet score was 2.7 points (of maximum 11) with most patients not achieving the recommended servings per week for fruits (1.6%), vegetables (1.0%), and unsalted nuts (12.2%). The intake of cereals was sufficient (43.3%). When compared with men, women consumed more fruits and less meat. Conclusions: This survey demonstrated that although healthy nutrition may have a positive impact on patients with PAD, the education and adherence to a Mediterranean Diet was inappropriate. Nutritional patterns should be more focused in future PAD studies to derive specific recommendations and nutritional programmes as well as patient education in clinical practice.

Effects of fluids vs. vasopressors on spinal cord microperfusion in hemorrhagic shock induced ischemia/reperfusion.

OBJECTIVE: Spinal cord injury induced by ischemia/reperfusion is a devastating complication of aortic repair. Despite developments for prevention and treatment of spinal cord injury, incidence is still considerably high majorly impacting patient outcome. Microcirculation is paramount for tissue perfusion and oxygen supply and often dissociated from macrohemodynamic parameters used to guide resuscitation. Effects of fluids vs. vasopressors in the setting of hemodynamic resuscitation on spinal cord microperfusion are unknown. Aim of this study was to compare the effects of vasopressor and fluid resuscitation on spinal cord microperfusion in a translational acute pig model of hemorrhagic shock induced ischemia/reperfusion injury. METHODS: We designed this study as prospective randomized explorative large animal study. We induced hemorrhagic shock in 20 pigs as a model of global ischemia/reperfusion injury. We randomized animals to receive either fluid or vasopressor resuscitation. We measured spinal cord microperfusion using fluorescent microspheres as well as laser-Doppler probes. We monitored and analyzed macrohemodynamic parameters and cerebrospinal fluid pressure. RESULTS: Spinal cord microperfusion decreased following hemorrhagic shock induced ischemia/reperfusion injury. Both fluids and vasopressors sufficiently restored spinal cord microperfusion. There were no important changes between groups (percentage changes compared to baseline: fluids 14.0 (0.31-27.6) vs. vasopressors 24.3 (8.12-40.4), p = .340). However, cerebrospinal fluid pressure was higher in animals receiving fluid resuscitation (percentage changes compared to baseline: fluids 27.7 (12.6-42.8) vs. vasopressors -5.56 ((-19.8)-8.72), p = .003). Microcirculatory resuscitation was in line with improvements of macrohemodynamic parameters. CONCLUSIONS: Both, fluids and vasopressors, equally restored spinal cord microperfusion in a porcine acute model of hemorrhagic shock induced ischemia/reperfusion injury. However, significant differences in cerebrospinal fluid pressure following resuscitation were present. Future studies should evaluate these effects in perfusion disruption induced ischemia/reperfusion conditions of microcirculatory deterioration.

Patients selected for dual pathway inhibition in clinical practice have similar characteristics and outcomes to those included in the COMPASS randomized trial: The XATOA Registry.

AIMS: To determine the characteristics of patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both, initiating dual pathway inhibition (DPI) using rivaroxaban 2.5 mg twice daily plus aspirin, and to report their clinical outcomes and bleeding rates in clinical practice compared to the COMPASS randomized trial, which provided the basis for using DPI in this patient population. METHODS AND RESULTS: XATOA is a prospective registry of 5532 patients: of which, 72.7% had CAD, 58.9% had PAD, and 31.6% had both. The mean age of patients was 68 years and 25.5% were women. The mean follow-up period was 15 months. The most frequently reported reason for initiating DPI was the presence of existing, worsening or newly diagnosed risk characteristics (n = 4753, 85.9%). Before initiating DPI, 75.3% received a single antiplatelet and 18.3% received various antiplatelet combinations. The incidence of major adverse cardiovascular events (MACE), major adverse limb events (MALE) and acute or severe limb ischaemia was 2.26, 3.57, and 1.54 per 100 patient-years, respectively, among the 5532 patients in XATOA. Corresponding rates in COMPASS were 2.18, 0.19, and 0.12 per 100 patient-years, respectively. Major bleeding rates were 0.95 and 1.67 per 100 patient-years in XATOA and COMPASS, respectively. CONCLUSION: High-risk vascular patients are prioritized for DPI in clinical practice, and rates of MACE are similar to COMPASS, but MALE rates are higher in XATOA, consistent with the greater proportion of PAD patients. Major bleeding rates were lower in XATOA. The findings provide support for favourable net clinical benefit of DPI in high-risk vascular patients. ONE-SENTENCE SUMMARY: The characteristics of patients initiated on dual pathway inhibition (DPI: rivaroxaban 2.5  mg twice daily plus aspirin) have not previously been defined in clinical practice and the XATOA registry findings demonstrate patient outcomes are consistent with those of the COMPASS trial, despite geographic differences in recruitment and the higher proportion of PAD patients.

Prevention of arterial and venous thrombotic events in symptomatic peripheral arterial disease patients after lower extremity revascularization in the VOYAGER PAD trial: Dual anticoagulant/antiplatelet regimen vs antiplatelet therapy alone.

BACKGROUND: Vascular disease burden after lower extremity revascularization (LER) comprises more than the first event, more vascular beds than the local arteries, and more than one clinical event type. OBJECTIVES: Assess total arterial and venous thrombotic burden after LER for symptomatic peripheral artery disease (PAD) and effect of low-dose anticoagulation added to low-dose antiplatelet therapy. PATIENTS/METHODS: VOYAGER PAD randomized 6564 symptomatic PAD patients undergoing LER to rivaroxaban 2.5 mg twice-daily or placebo on aspirin background. Marginal proportional-hazards models used to generate treatment hazard ratios and associated 95% CIs for first and total events; non-thrombotic deaths treated as competing terminal events. Incidence rates calculated as number of events per 100 patient-years follow-up. RESULTS: Over 2.5 years (median), first and total thrombotic event rates: 7.1 and 10.3 events/100 patient-years, respectively, in placebo group. Two-thirds (925/1372) of total thrombotic events (arterial 95%, venous 5%) were nonfatal first events. Nearly one-third of patients with first event had a second arterial or venous thrombotic event. Rivaroxaban plus aspirin reduced first and total arterial and venous thrombotic events to 5.4 and 7.9 events/100 patient-years, respectively, a reduction in total thrombotic events over aspirin of 23% (HR: 0.77, 95%CI: 0.67-0.89, p = .0005), preventing 6.1 total arterial and venous thrombotic events at 3 years. CONCLUSIONS: Assessing total arterial and venous thrombotic events, not just first events, provides more complete information about disease burden and absolute on-treatment impact. Following LER, judicious modulation of more than one coagulation pathway can provide broader benefit than intensifying inhibition of one hemostatic system component.

Editor's Choice - Update of the European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia in Light of the COVID-19 Pandemic, Based on a Scoping Review of the Literature.

OBJECTIVE: To perform a scoping review of how patients with COVID-19 are affected by acute limb ischaemia (ALI) and evaluate the recommendations of the 2020 ESVS ALI Guidelines for these patients. METHODS: Research questions were defined, and a systematic literature search was performed following the PRISMA guidelines. Abstracts and unpublished literature were not included. The definition of ALI in this review is in accordance with the ESVS guidelines. RESULTS: Most identified papers were case reports or case series, although population based data and data from randomised controlled trials were also identified. In total, 114 unique and relevant papers were retrieved. Data were conflicting concerning whether the incidence of ALI increased, or remained unchanged, during the pandemic. Case reports and series reported ALI in patients who were younger and healthier than usual, with a greater proportion affecting the upper limb. Whether or not this is coincidental remains uncertain. The proportion of men/women affected seems unchanged. Most reported cases were in hospitalised patients with severe COVID-19. Patients with ALI as their first manifestation of COVID-19 were reported. Patients with ALI have a worse outcome if they have a simultaneous COVID-19 infection. High levels of D-dimer may predict the occurrence of arterial thromboembolic events in patients with COVID-19. Heparin resistance was observed. Anticoagulation should be given to hospitalised COVID-19 patients in prophylactic dosage. Most of the treatment recommendations from the ESVS Guidelines remained relevant, but the following were modified regarding patients with COVID-19 and ALI: 1) CTA imaging before revascularisation should include the entire aorta and iliac arteries; 2) there should be a high index of suspicion, early testing for COVID-19 infection and protective measures are advised; and 3) there should be preferential use of local or locoregional anaesthesia during revascularisation. CONCLUSION: Although the epidemiology of ALI has changed during the pandemic, the recommendations of the ESVS ALI Guidelines remain valid. The above mentioned minor modifications should be considered in patients with COVID-19 and ALI.

Early outcomes of t-Branch off-the-shelf multibranched stent graft in urgent and emergent repair of thoracoabdominal aortic aneurysms.

OBJECTIVE: We compared the outcomes between elective, urgent, and emergent treatment of thoracoabdominal aortic aneurysms (TAAAs) using the t-Branch off-the-shelf multibranched stent graft (Cook Medical, Bloomington, Ind). METHODS: All consecutive patients treated for TAAAs using the t-Branch between September 2012 and June 2019 were included in the present study. The patients were divided into three groups according to the urgency of repair: (1) elective, (2) urgent, and (3) emergent. The periprocedural details and 30-day outcomes were analyzed. Survival and reinterventions were analyzed using Kaplan-Meier curves and log-rank tests. RESULTS: The t-Branch stent graft was used for 100 patients during the study period. Of the 100 patients, 30 (73% male; mean age, 65 ± 10 years) were treated electively, 49 (54% male; mean age, 72 ± 7 years) urgently, and 21 (81% male; mean age, 75 ± 9 years) emergently. Transfemoral access with a steerable sheath was used more frequently for target vessel catheterization in the elective group (57%) than in the urgent (8%) and emergent (5%) groups (P = .021). The total number of targeted vessels was 111 of 120 (93%) in the elective group vs 185 of 196 (94%) in the urgent group and 82 of 84 (98%) in the emergent group. The corresponding technical success rates were 97% (29 of 30), 98% (48 of 49), and 95% (20 of 21). The median intensive care unit stay was shorter in the elective group (3 days; range, 1-41 days) than in the urgent group (5 days; range, 1-41 days) and emergent group (11 days; range, 3-37 days; P = .004). The 30-day mortality rate was lower in the elective group (2 of 30; 7%) than in the urgent group (8 of 49; 16%) and emergent group (5 of 21; 24%; P = .049). The acute kidney injury rate was lower in the elective group (2 of 30; 7%) than in the urgent group (11 of 49; 22%) and emergent group (8 of 21; 38%; P = .002). The spinal cord ischemia rate was also lower in the elective group (5 of 30; 17%) than in the urgent group (5 of 49; 10%) and emergent group (8 of 21; 38%; P = .051). The median follow-up was 8 months (interquartile range, 3.2-18.5 months). The cumulative survival rate was 95%, 87%, and 87% at 6, 12, and 24 months, respectively. The cumulative freedom from reintervention during follow-up was 92%, 86%, and 77% at 6, 12, and 24 months, respectively. CONCLUSIONS: The technical success of TAAA repair using t-Branch stent graft was not affected by an urgent or emergent presentation. However, the occurrence of worse periprocedural morbidity and mortality was significantly associated with an urgent or emergent presentation.

Early and Mid-Term Durability of Surgeon-Modified and Custom-Made Fenestrated Devices for the Treatment of Complex Aortic Pathology.

BACKGROUND: Fenestrated endovascular aneurysm repair (F-EVAR) has allowed successful treatment of patients with complex aortic aneurysms. Custom-made devices (CMDs) are manufactured by companies and tailored to the patient's anatomy to incorporate target vessels, while there is also the "off label" alternative with the devices modified by a surgeon in the operating room: surgeon-modified FEVAR (sm-FEVAR). This study aims to present and compare technical durability of CMDs- and sm-FEVAR for complex abdominal and thoracoabdominal aortic pathologies. METHODS: A retrospective cohort study was undertaken including all consecutive patients treated with sm- or CMD-FEVAR during a 3-year period in a single center. Only cases with at least 3 reno-visceral target vessels were included. Primary outcomes were technical success, and freedom from endoleak (EL) (Ia or III; all branch related) and re-intervention during follow-up period. Mortality and morbidity were also recorded. RESULTS: Thirty-two sm-FEVAR patients (81,3% male) and 79 CMD-FEVAR patients (77,2% male) were included. Indication for sm-FEVAR was exclusively urgent, while all CMD- FEVAR were elective. Technical success was similar in sm-FEVAR (100%) and CMD-FEVAR (98,7%) (P = 0.523). Mean follow-up was 16.3 ± 13 and 20 ± 17.3 months for sm-FEVAR and CMD- FEVAR, respectively (P = 0.28). The freedom from EL Ia rate was 91.7% [standard error (SE) 5.7%] at 12 months in sm-FEVAR, while it was 97.7% (SE 2.2%) and 92.3% (SE 4.3%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.69). The freedom from EL III rate was 95.5% (SE 4.4%) and 88% (SE 8.2%) at 12 and 24 months, respectively in sm-FEVAR, while it was 92.1% (SE 3.8%) and 89.2% (SE 4.7%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.68). The freedom from re-intervention rate was 91.6% (SE 5.7%) and 84.6% (SE 8.6%) at 12 and 24 months, respectively in sm-FEVAR, while it was 91.7% (SE 4%) and 83.4% (SE 5.9%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.90). The survival rate was 87.5% (5.8%) and 76.3% (7.9%) at 1 and 12 months, respectively in sm-FEVAR, while it was 93.7% (2.7%) at 1 month in CMD-FEVAR without any other death during FU period. No bridging stent occlusions were noted during follow-up period in any patient. CONCLUSION: Sm-FEVAR offers good technical success and mid-term clinical outcomes in urgent cases of complex aortic pathologies. Its durability is acceptable and comparable to CMD-FEVAR with a relatively low re-intervention rate.

Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD.

BACKGROUND: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. METHODS: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. RESULTS: Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59). CONCLUSIONS: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Safety and Effectiveness of Paclitaxel Drug-Coated Devices in Peripheral Artery Revascularization: Insights From VOYAGER PAD.

BACKGROUND: Paclitaxel drug-coated devices (DCDs) were developed to improve lower extremity revascularization (LER) patency in peripheral artery disease (PAD) but have been associated with long-term mortality. OBJECTIVES: This study assessed DCD safety and effectiveness in LER for PAD. METHODS: VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) randomized patients with PAD who underwent LER to rivaroxaban or placebo. The primary VOYAGER PAD study efficacy and safety outcomes were composite cardiovascular and limb events and Thrombolysis In Myocardial Infarction major bleeding. For prespecified DCD analyses, primary safety and effectiveness outcomes were mortality and unplanned index limb revascularization (UILR). Major adverse limb events (MALE) were a secondary outcome. Inverse probability treatment weighting was used to account for each subject's propensity for DCD treatment. Effects of rivaroxaban were assessed with Cox proportional hazards models. RESULTS: Among 4,316 patients who underwent LER, 3,478 (80.6%) were treated for claudication, and 1,342 (31.1%) received DCDs. Median follow-up was 31 months, vital status was ascertained in 99.6% of patients, and there were 394 deaths. After weighting, DCDs were not associated with mortality (HR: 0.95; 95% CI: 0.83-1.09) or MALE (HR: 1.08; 95% CI: 0.90-1.30) but were associated with reduced UILR (3-year Kaplan-Meier: 21.5% vs 24.6%; HR: 0.84; 95% CI: 0.76-0.92). Irrespective of DCD use, consistent benefit of rivaroxaban for composite cardiovascular and limb events (Pinteraction = 0.88) and safety of rivaroxaban with respect to bleeding (Pinteraction = 0.57) were observed. CONCLUSIONS: In >4,000 patients with PAD who underwent LER, DCDs were not associated with mortality or MALE but were associated with persistent reduction in UILR. These findings provide insight into the safety and effectiveness of DCDs in PAD. (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD [VOYAGER PAD]; NCT02504216).