New Horizons in Peripheral Artery Disease.

Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.

Predictors of outcome in diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia.

OBJECTIVE: The incidence of chronic limb-threatening ischemia in diabetic patients is increasing. The factors influencing outcome after infrapopliteal revascularization in these patients are largely unknown. Therefore, this study aims to identify the impact of perioperative glucose control on the long-term outcomes in this patient cohort, and furthermore to identify other factors independently associated with outcome. METHODS: Consecutive diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia were identified. Patients' demographics, procedural details, daily capillary blood glucose, and hemoglobin A1C levels were collected and analyzed against the study end points using Kaplan-Meier and Cox regression analysis. RESULTS: A total of 437 infrapopliteal target vessels were successfully crossed in 203 patients. Amputation-free survival by Kaplan-Meier (estimate (standard error)%) was 74 (3.3)% and 63 (3.7)%, primary patency was 61 (4.2)% and 50 (4.9)%, assisted primary patency was 69 (5.2)% and 55 (6.1)%, and secondary patency was 71 (3.8)% and 59 (4.1)% at 1 year and 2 years, respectively. Cox regression analysis showed high perioperative capillary blood glucose levels to be an independent predictor of binary restenosis (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.31-1.1.78; P = .015). Postprocedural dual-antiplatelet therapy was found to be an independent predictor of amputation-free survival (HR, 1.69; 95% CI, 1.04-2.75; P = .033), and freedom from major adverse limb events (HR: 1.96; 95% CI, 1.16-3.27; P = .023) and baseline estimated glomerular filtration rate was significantly associated with better amputation-free survival (HR, 0.52; 95% CI, 0.31-0.87; P = .014). CONCLUSIONS: Poor perioperative glycemic control is associated with a higher incidence of restenosis after infrapopliteal revascularization in diabetic patients. Dual antiplatelet therapy is associated with better outcomes in this group.

Impact of Longer Hemodialysis Vintage with Higher Serum Phosphorus Level on Clinical Outcomes in Patients with Chronic Limb-Threatening Ischemia Presenting Tissue Loss after Endovascular Therapy.

AIMS: Hemodialysis vintage and serum phosphorus levels adversely affect outcomes in patients on hemodialysis. Whether these factors have a similar prognostic impact on patients who are on hemodialysis and have chronic limb-threatening ischemia (CLTI) has not been systematically studied. We aimed to explore the risk factors, including hemodialysis vintage and serum phosphorus levels, on clinical outcomes after endovascular therapy (EVT) in hemodialysis patients with CLTI. METHODS: The current study rerospectively analyzed 374 hemodialysis patients with CLTI presenting with ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 68.2%, Rutherford 5: 75.9%, 6: 24.1%, WIfI stage 4: 50.0%) primarily treated with EVT between April 2007 and December 2016. The primary outcome measure was 1-year amputation-free survival (AFS), while the secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. RESULTS: Multivariate analysis significantly associated longer hemodialysis vintages with higher serum phosphorus levels (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.394-0.910; p=0.016) with 1-year AFS. Longer vintages for hemodialysis with higher serum phosphorus levels were marginally, but not significantly, associated with 1-year wound healing. (HR, 0.684; 95% CI, 0.467-1.000; p=0.050). CONCLUSION: Longer hemodialysis vintages with higher serum phosphorus levels adversely affect outcomes after EVT for hemodialysis patients with CLTI presenting with ischemic tissue loss.

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).

Epidemiology of Peripheral Artery Disease and Polyvascular Disease.

Atherosclerotic lower extremity peripheral artery disease (PAD) is increasingly recognized as an important cause of cardiovascular morbidity and mortality that affects >230 million people worldwide. Traditional cardiovascular risk factors, including advanced age, smoking, and diabetes, are strongly linked to an increase risk of PAD. Although PAD has been historically underappreciated compared with coronary artery disease and stroke, greater attention on PAD in recent years has led to important new epidemiological insights in the areas of thrombosis, inflammation, dyslipidemia, and microvascular disease. In addition, the concept of polyvascular disease, or clinically evident atherosclerosis in multiple arterial beds, is increasingly identified as a particularly malignant cardiovascular disease worthy of special clinical attention and further study. It is noteworthy that PAD may increase the risk of adverse outcomes in similar or even greater magnitude than coronary disease or stroke. In this review, we highlight important new advances in the epidemiology of PAD with a particular focus on polyvascular disease, emerging biomarkers, and differential risk pathways for PAD compared with other atherosclerotic diseases.

The impact of diabetes mellitus on major amputation among patients with chronic limb threatening ischemia undergoing elective endovascular therapy- a nationwide propensity score adjusted analysis.

AIM: To investigate the risk of major amputation after elective endovascular therapy in patients with chronic limb threatening ischemia (CLTI) comparing patients with and without diabetes mellitus (DM). METHODS: In this nationwide cohort study, all patients registered in the Swedish Vascular Register after elective endovascular therapy for CLTI caused by infra-inguinal arterial disease from 2010 to 2014 were included. Among 4578 individuals, 2251 had DM and were registered in the National Diabetes Register between 2009 and 2014. A propensity score adjusted Cox regression analysis was conducted to compare outcomes between groups. Median follow-up was 4.0 and 3.6 years for patients with DM and without DM, respectively. RESULTS: The incidence rates of major amputation and acute myocardial infarction (AMI) were 43% (95% CI 1.23-1.67) and 37% (95% CI 1.13-1.67) higher, respectively, among patients with DM compared to patients without DM. There was no difference in mortality (HR 1.04, 95% CI 0.95-1.14). CONCLUSIONS: Patients with DM had a higher risk of major amputation and AMI compared to those without DM after elective endovascular therapy for CLTI. Prevention of DM with CLTI is of utmost importance to reduce the risk of adverse limb and cardiovascular outcomes.

Effects of PCSK9 Inhibitor on Favorable Limb Outcomes in Patients with Chronic Limb-Threatening Ischemia.

AIM: The aim of this study was to examine the effects of evolocumab on favorable limb events in patients with chronic limb-threatening ischemia (CLTI). METHODS: A single-center, prospective observational study was performed on 30 patients with CLTI. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated (E) group ( n=14) and evolocumab non-treated (non-E) group (n=16). The primary outcome was 12-month freedom from major amputation. The secondary outcomes were 12-month amputation-free survival (AFS), overall survival (OS), and wound-free limb salvage. The mean follow-up period was 18±11 months. RESULTS: No significant difference was detected between the two groups for the 12-month freedom from major amputation (log-rank p=0.15), while the 12-month AFS rate was significantly higher in the E group than that in the non-E group (log-rank p=0.02). The 12-month OS rate in the E group was shown a tendency for improvement, as compared with that in the non-E group (log-rank p=0.056). Evolocumab administration was not associated with a significant change in freedom from major amputation (HR, 0.23, 95% CI, 0.03-2.07, p=0.19). However, evolocumab administration was related to a tendency for improvement of AFS and OS (HR, 0.13, 95% CI, 0.02-1.06, p=0.056; HR, 0.16, 95% CI, 0.02-1.37, p=0.09, respectively). Moreover, The E group had a higher proportion of wound-free limb salvage at 12 months (92% vs. 42%, p=0.03). CONCLUSION: Evolocumab administration was associated with a better AFS outcome in patients with CLTI. Long-term administration of evolocumab over 12 months contributed to improving proportion of wound-free limb salvage.