Cohort Study Examining the Association of Immunosuppressant Drug Prescription With Major Adverse Cardiovascular and Limb Events in Patients With Peripheral Artery Disease.

AIM: Immune activation is strongly implicated in atherosclerotic plaque instability, however, the effect of immunosuppressant drugs on cardiovascular events in patients with peripheral artery disease (PAD) is not known. The aim of this study was to assess whether prescription of one or more immune suppressant drugs was associated with a lower risk of major adverse cardiovascular (MACE; i.e. myocardial infarction, stroke or cardiovascular events) or limb events (MALE; i.e. major amputation or requirement for peripheral revascularization) in patients with PAD. METHODS: A total of 1506 participants with intermittent claudication (n = 872) or chronic limb threatening ischemia (CLTI; n = 634) of whom 53 (3.5%) were prescribed one or more immunosuppressant drugs (prednisolone 41; methotrexate 17; leflunomide 5; hydroxychloroquine 3; azathioprine 2; tocilizumab 2; mycophenolate 1; sulfasalazine 1; adalimumab 1) were recruited from 3 Australian hospitals. Participants were followed for a median of 3.9 (inter-quartile range 1.2, 7.3) years. The association of immunosuppressant drug prescription with MACE or MALE was examined using Cox proportional hazard analyses. RESULTS: After adjusting for other risk factors, prescription of an immunosuppressant drug was associated with a significantly greater risk of MACE (Hazard ratio, HR, 1.83, 95% confidence intervals, CI, 1.11, 3.01; P = 0.017) but not MALE (HR 1.32, 95% CI 0.90, 1.92; P = 0.153). In a sub-analysis restricted to participants with CLTI findings were similar: MACE (HR 2.44, 95% CI 1.32, 4.51; P = 0.005); MALE (HR 1.38, 95% CI 0.87, 2.19; P = 0.175); major amputation (HR 1.37, 95% CI 0.49, 3.86; P = 0.547). CONCLUSIONS: This cohort study suggested that immunosuppressant drug therapy is associated with a greater risk of MACE amongst patients with PAD.

Reinterventions in Patients with Claudication and Chronic Limb Threatening Ischemia.

BACKGROUND: Patients with peripheral artery disease (PAD) present with claudication or chronic limb threatening ischemia (CLTI). CLTI patients have a more advanced stage of atherosclerosis and increased comorbidities compared to claudicants, and are at an elevated risk of major amputation and mortality after lower extremity revascularization (LER). However, the frequency of reinterventions for claudication and CLTI have not been compared. Our hypothesis is that patients with CLTI undergo more frequent reinterventions to prevent major amputation. METHODS: A single-center retrospective chart review of consecutive patients undergoing lower extremity revascularization (LER) for PAD in 2013-2015 was performed. Patients were stratified based on indication for revascularization into claudication or CLTI. Patient characteristics, outcomes, and reinterventions were compared between the 2 groups. RESULTS: There were 826 patients undergoing LER and 44% (N = 361) had CLTI. Patients treated for CLTI were more likely to be smokers (P < 0.001), to have diabetes (P< 0.001), chronic renal insufficiency (P< 0.001), end stage renal disease (P< 0.001), and cardiac disease (P< 0.001). CLTI patients were less likely to be on optimal medical management as reflected by decreased rate of aspirin (P< 0.001), ADP receptor/P2Y12 inhibitors (P< 0.001), and statins (P< 0.001) compared to patients with claudication. Patients with CLTI had significantly higher major amputation (3.7% vs. 0.2%, P< 0.001) and mortality (1.4% vs. 0.2%, P = 0.092) at 30 days. At long-term follow up, patients with CLTI had higher rates of major amputation (15.5% vs. 1.3%, P < 0.001) and mortality (37.1% vs. 18.1%, P < 0.001) compared to patients with claudication. There was a significant difference in mean follow-up time between the 2 cohorts (claudication: 3.7 ± 1.5 years versus CLTI: 2.6 ± 1.8 years, P < 0.001). There was no significant difference in the ipsilateral reintervention rate between the 2 groups (claudication: 39.6% vs. CLTI: 42.7%, P = 0.37) or the mean number of ipsilateral reinterventions (claudication: 2.0 ± 1.6 vs. CLTI: 2.0 ± 1.7). However, after adjusting for follow-up time, the mean number of reinterventions per year was significantly higher for CLTI patients compared to patients with claudication (1.4 ± 2.2 vs. .6 ± 0.7 intervention per year, P < 0.001). CONCLUSIONS: Patients undergoing LER for CLTI undergo more frequent reinterventions over time compared to patients treated for claudication. Research on reinterventions after LER should include reporting of the frequency of reintervention adjusted for the follow up period in addition to the reintervention rate defined as the percentage of patients undergoing reintervention.

Efficacy and one-year outcomes of Luminor® paclitaxel-coated drug-eluting balloon in the treatment of popliteal artery atherosclerosis lesions.

PURPOSE: Reporting outcomes with a new generation paclitaxel eluting balloon (Luminor®; iVascular, Vascular, S.L.U., Barcelona, Spain) in the popliteal district. Endovascular treatment of popliteal artery atherosclerotic disease is still debated without definitive evidences. METHODS: From January to June 2019, patients' data presenting popliteal artery atherosclerotic diseases and treated with the Luminor® (iVascular) drug eluting balloon (DEB) were prospectively collected. Critical limb ischemia (CLI) or severe claudication associated with popliteal artery stenosis >50% were the inclusion criteria. Measured outcomes were technical success, early and late results; including mortality, morbidity, symptoms recurrence, amputation, ankle-brachial index (ABI), survival, primary patency, secondary patency, freedom from restenosis. Median follow-up was 22.43 ± 4 (mean:21.58; IQR:20-24) months. RESULTS: Of the 33 included patients, 28 (85%) were diagnosed with CLI, with a mean preoperative run-off score of 5.39 (r:0-10; SD:3) and a chronic popliteal occlusion in 21 (64%). Technical success was achieved in all cases. Perioperative mortality was observed in 1 (3%) patient and perioperative complications in 2 (6%). During the follow-up were reported 2 symptoms recurrence; a significant ABI increase (0.57; IQR:0.41-0.47 vs. 0.69; IQR:0.50-0.67; P < 0.01); 1 (3%) major and 2 (6%) minor amputations. Estimated 24 months survival, primary patency, secondary patency, and freedom from restenosis were 97%, 96.9%, 100%, and 93.8% respectively. CONCLUSIONS: In this prospective study, the use of the Luminor® (iVascular) was safe and effective in addressing atherosclerotic popliteal artery lesions. Larger studies with longer term-outcomes are required to assess the durability of this device in the popliteal artery.

Angiogenin-A Proposed Biomarker for Cardiovascular Disease-Is Not Associated With Long-Term Survival in Patients With Peripheral Artery Disease.

We evaluated angiogenin as a prospective biomarker in peripheral artery disease (PAD) patients with and without claudication symptoms. A pilot study suggested an elevation of angiogenin in critical limb ischemia. However, in PAD patients, the predictive value of angiogenin has not yet been evaluated. For this purpose, 342 patients with PAD (age: 69 ± 10 years, 34.5% women) were followed-up for 7 years in a cross-sectional study. Angiogenin was measured by enzyme-linked immunosorbent assay. All-cause and cardiovascular mortality were analyzed by Cox regression. Angiogenin levels were higher in men (P = .001) and were associated with patient waist-to-hip ratio (P < .001), fasting triglycerides (P = .011), and inversely with estimated glomerular filtration rate (P = .009). However, angiogenin showed no association with age, characteristics of diabetes, markers of lipid metabolism, or C-reactive protein. Angiogenin did not correlate with markers of angiogenesis such as vascular endothelial growth factor, angiopoietin-2, or tie-2. Furthermore, angiogenin was not associated with PAD Fontaine stages or with patient ankle-brachial index in addition to all-cause mortality (hazard ratio [HR] = 1.09 [95% CI: 0.89-1.34]) or cardiovascular morality (HR = 1.05 [0.82-1.35]). These results suggest that angiogenin does not provide further information regarding outcome prediction in patients with PAD.

A health insurance claims analysis on the effect of female sex on long-term outcomes after peripheral endovascular interventions for symptomatic peripheral arterial occlusive disease.

OBJECTIVE: Several reports have addressed sex disparities in peripheral arterial occlusive disease (PAOD) treatment with inconclusive or even conflicting results. However, most previous studies have neither been sufficiently stratified nor used matching or weighting methods to address severe confounding. In the present study, we aimed to determine the disparities between sexes after percutaneous endovascular revascularization (ER) for symptomatic PAOD. METHODS: Health insurance claims data from the second-largest insurance fund in Germany, BARMER, were used. A large cohort of patients who had undergone index percutaneous ER of symptomatic PAOD from January 1, 2010 to December 31, 2018 were included in the present study. The study cohort was stratified by the presence of intermittent claudication, ischemic rest pain, and wound healing disorders. Propensity score matching was used to adjust for confounding through differences in age, treated vessel region, comorbidities, and pharmacologic treatment. Sex-related differences regarding cardiovascular event-free survival, amputation-free survival, and overall survival within 5 years of surgery were determined using Kaplan-Meier time-to-event curves, log-rank test, and Cox regression analysis. RESULTS: In the present study, 50,051 patients (47.2% women) were identified and used to compose a matched cohort of 35,232 patients. Among all strata, female patients exhibited lower mortality (hazard ratio [HR], 0.69-0.90), fewer amputations or death (HR, 0.70-0.89), and fewer cardiovascular events or death (HR, 0.78-0.91). The association between female sex and improved long-term outcomes was most pronounced for the patients with intermittent claudication. CONCLUSIONS: In the present propensity score-matched analysis of health insurance claims, we observed superior cardiovascular event-free survival, amputation-free survival, and overall survival during 5 years of follow-up after percutaneous ER in women with symptomatic PAOD. Future studies should address sex disparities in the open surgical treatment of PAOD to illuminate whether the conflicting data from previous reports might have resulted from insufficient stratification of the studies.

Femoral-popliteal peripheral artery disease: From symptom presentation to management and treatment controversies.

Peripheral artery disease (PAD) is a common condition with increasing prevalence domestically and worldwide. Patients with PAD have a poor prognosis, as PAD is associated with high rates of myocardial infarction, ischemic stroke, and cardiovascular disease death. The primary symptom of PAD, claudication, significantly reduces quality of life and functional status and is associated with depression. In addition to several advances in medications for PAD over the last decade, endovascular device therapy has seen a significant breakthrough in the form of paclitaxel-coated devices (PCDs), which significantly reduce rates of restenosis relative to non-PCDs, a finding which has been demonstrated in numerous randomized clinical trials. After their introduction to the market in 2012 (paclitaxel-eluting stents) and 2014 (paclitaxel-coated balloons) their use surged as they replaced non-PCDs and were designated the first-line endovascular therapy by society guidelines. This trend was abruptly reversed, however, after a meta-analysis of summary-level data was published in December of 2018 that reported an elevated mortality associated with PCDs compared with non-PCDs 2-5 years after treatment. This meta-analysis has been criticized for considerable methodological flaws. The Food and Drug Administration conducted a review and concluded that insufficient data existed to make a definitive statement regarding the safety of PCDs. They called for restriction of the use of PCDs to the highest-risk patient populations. At the same time, the FDA deemed pursuing new RCTs to better evaluate PCDs unfeasible due to the high numbers of patients and long follow-up time that would be required. In this setting, real-world data emerged as a powerful source of information for the evaluation of PCDs. Real-world data offers advantages over randomized-controlled trials including expeditious access to and analysis of data and the availability of large numbers of patients. Several retrospective observational studies demonstrate no difference in long-term all-cause mortality in patients treated with PCDs relative to those treated with non-PCDs. This paclitaxel controversy has illustrated the critical role that real-world data is assuming in long-term safety monitoring of medical devices.

Association between Physical Activity and Mortality in Patients with Claudication.

PURPOSE: This study aimed to determine the association between light-intensity physical activity and the incidence of all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD) limited by claudication followed for up to 18.7 yr. METHODS: A total of 528 patients with PAD and claudication were screened in Baltimore between 1994 and 2002, and 386 were deemed eligible for the study. At baseline, patients were classified into three physical activity groups: 1) physically sedentary, 2) light intensity, and 3) moderate to vigorous intensity based on a questionnaire. All-cause and cardiovascular mortality of patients through December 2014 was determined using the National Death Index and the U.S. Department of Veterans Affairs and the U.S. Department of Defense Suicide Data Repository. RESULTS: Median survival time was 9.9 yr (interquartile range, 4.9-15.7 yr; range, 0.38-18.7 yr). During follow-up, 257 patients (66.6%) died, consisting of 40/48 (83.3%) from the sedentary group, 135/210 (64.3%) from the light-intensity group, and 82/128 (64.0%) from the moderate- to vigorous-intensity group. For all-cause mortality, light-intensity activity status (hazard ratio [HR] = 0.523, P = 0.0007) and moderate- to vigorous-intensity status (HR = 0.425, P < 0.0001) were significant predictors. During follow-up, 125 patients died because of cardiovascular causes (32.4%), in which light-intensity activity status (HR = 0.511, P = 0.0113) and moderate- to vigorous-intensity activity status (HR = 0.341, P = 0.0003) were significant predictors. CONCLUSIONS: Light-intensity physical activity is associated with nearly 50% lower risk of all-cause and cardiovascular mortality in high-risk patients with PAD and claudication. Furthermore, moderate- to vigorous-intensity physical activity performed regularly is associated with 58% and 66% lower risk of all-cause and cardiovascular mortality, respectively. The survival benefits associated with light-intensity physical activity make it a compelling behavioral intervention that extends beyond improving ambulation.

Characteristics and outcomes of patients with peripheral artery disease undergoing endovascular revascularization: A community hospital perspective.

BACKGROUND: There are limited data on outcomes for patients with peripheral artery disease undergoing endovascular revascularization by multi-disciplinary teams in a community hospital setting. METHODS: From January 2015 through December 2015, we assembled a multi-disciplinary program comprised of cardiologists, surgeons, radiologists, nurses, and administrative staff for managing patients with peripheral artery disease undergoing endovascular revascularization. Demographic, procedural, and outcomes data were collected with use of a template from the Society for Vascular Surgery Vascular Quality Initiative database. We compared characteristics and outcomes of patients with intermittent claudication and critical limb ischemia. We used Kaplan-Meier methods to estimate the rate of overall survival and freedom from rehospitalization between groups. RESULTS: After excluding patients with acute limb ischemia (n = 5), peripheral intervention to the upper extremity (n = 6), or abdominal aorta (n = 11), there were 82 patients in the study cohort; 45 had intermittent claudication and 37 had critical limb ischemia. Baseline and procedural characteristics were similar between groups, although critical limb ischemia patients were more likely to have hyperlipidemia (75.7% vs. 53.3%, P = .42). Procedural success was achieved in 91.3% of cases. Actionable access site bleeding occurred in 2.4% of patients. High rates of aspirin (91.5%) and statin (87.8%) were noted at discharge. After two years of post endovascular revascularization, survival was 57.5% for critical limb ischemia patients and 94.4% for intermittent claudication patients (P < .001). Freedom from rehospitalization was 32.7% for critical limb ischemia patients and 83.5% for intermittent claudication patients (P < .001). CONCLUSIONS: We found that favorable outcomes may be achieved with a multi-disciplinary peripheral artery disease program at community hospitals. The incorporation of quality improvement practices may further help to develop standardized and regionalized approaches to care delivery for patients with peripheral artery disease.

Lower Limb Revascularization for Peripheral Arterial Disease in 10,951 Procedures over 11 years in a Public Health System: A Descriptive Analysis of the Largest Brazilian City.

BACKGROUND: Worldwide, peripheral arterial disease (PAD) is a disease with high morbidity, affecting more than 200 million people. Our objective was to analyze the surgical treatment for PAD performed in the Unified Health System of the city of São Paulo during the last 11 years based on publicly available data. METHODS: The study was conducted with data analysis available on the TabNet platform, belonging to the DATASUS. Public data (government health system) from procedures performed in São Paulo between 2008 and 2018 were extracted. Sex, age, municipality of residence, operative technique, number of surgeries (total and per hospital), mortality during hospitalization, mean length of stay in the intensive care unit and amount paid by the government system were analyzed. RESULTS: A total of 10,951 procedures were analyzed (either for claudicants or critical ischemia-proportion unknown); 55.4% of the procedures were performed on males, and in 50.60%, the patient was older than 65 years. Approximately two-thirds of the patients undergoing these procedures had residential addresses in São Paulo. There were 363 in-hospital deaths (mortality of 3.31%). The hospital with the highest number of surgeries (n = 2,777) had lower in-hospital mortality (1.51%) than the other hospitals. A total of $20,655,272.70 was paid for all revascularizations. CONCLUSIONS: Revascularization for PAD treatment has cost the government system more than $20 million over 11 years. Endovascular surgeries were performed more often than open surgeries and resulted in shorter hospital stays and lower perioperative mortality rates.

The cost-effectiveness of intensive low-density lipoprotein cholesterol lowering in people with peripheral artery disease.

BACKGROUND: People with peripheral artery disease are at a high risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Randomized controlled trials suggest that intensive lowering of low-density lipoprotein cholesterol (LDL-C) with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is an effective strategy to prevent these events. This study estimated the potential benefit and cost-effectiveness of administrating PCSK9 inhibitors to a cohort of participants with peripheral artery disease. METHODS: A total of 783 participants with intermittent claudication (IC; n = 582) or chronic limb-threatening ischemia (CLTI; n = 201) were prospectively recruited from three hospitals in Australia. Serum LDL-C was measured at recruitment, and the occurrence of MACE and MALE was recorded over a median (interquartile range) follow-up of 2.2 years (0.3-5.7 years). The potential benefit of administering a PCSK9 inhibitor was estimated by calculating the absolute risk reduction and numbers needed to treat (NNT) based on relative risk reductions reported in published randomized trials. The incremental cost-effectiveness ratio per quality-adjusted life year gained was estimated. RESULTS: Intensive LDL-C lowering was estimated to lead to an absolute risk reduction in MACE of 6.1% (95% confidence interval [CI], 2.0-9.3; NNT, 16) and MALE of 13.7% (95% CI, 4.3-21.5; NNT, 7) in people with CLTI compared with 3.2% (95% CI, 1.1-4.8; NNT, 32) and 5.3% (95% CI, 1.7-8.3; NNT, 19) in people with IC. The estimated incremental cost-effectiveness ratios over a 10-year period were $55,270 USD and $32,800 USD for participants with IC and CLTI, respectively. CONCLUSIONS: This analysis suggests that treatment with a PCSK9 inhibitor is likely to be cost-effective in people with CLTI.

Rotational atherectomy with adjunctive balloon angioplasty in calcified chronic total occlusions of superficial femoral artery.

OBJECTIVES: The aim was to report the mid-term outcomes of Jetstream™ rotational atherectomy device in complex femoropopliteal lesions. METHODS: Between November 2016 and April 2018, 55 patients who were treated with rotational atherectomy and adjunctive balloon angioplasty due to complex femoropopliteal lesions were retrospectively scanned. RESULTS: Fifty-five patients who underwent endovascular treatment with rotational atherectomy for chronic total occlusive femoropopliteal lesions were included in the study. Technical success rate was 100%. The mean age was 63 (±10.5) years. The cohort included 25 (45.4%) diabetics and 45 (81.8%) current smokers. The mean length of the lesions was 20.8 ± 11.2 cm. Chronic total occlusive lesions were detected in 35 (63.6%) patients, and mixed-type steno-occlusive lesions were detected in 20 patients (36.4%). Thirty-three (60%) lesions were moderate or severely calcified. Adjunctive balloon angioplasty was performed with plain old balloon angioplasty (POBA) on 31 (56.4%) patients and with drug-coated balloon angioplasty on 24 (43.6%) patients. After adjunctive balloon angioplasty, flow limiting dissection was observed in 20 (36.3%) patients, and 17 (30.9%) patients needed stent implantation. The Kaplan-Meier analysis method estimated that the overall primary patency rates at 12 and 24 months were 81.8% and 70.9%, respectively. Overall, secondary patency rates at 12 and 24 months were 94.5% and 80%. No statistically significant differences of 24-month primary patency and secondary patency rates were found between patients treated with drug-coated balloon angioplasty and POBA as an adjunctive therapy, even though primary patency (83.3% vs. 61.3%, p = .06) and secondary patency (91.7% vs. 71%, p = .56) rates of drug-coated balloon angioplasty were slightly higher than POBA. Patients with claudication had better primary patency (90.5% vs. 58.8%, p = .001) and secondary patency (100% vs. 67.6%, p = .004) rates than patients with critical limb ischemia at 24 months. Significant differences between patients who did and did not stop smoking were found in 24-month primary patency (57% vs. 88%, p = .007) and secondary patency (67% vs. 96%, p = .007). Six patients underwent unplanned amputation. There were eight (14.5%) mortalities during follow-up. CONCLUSIONS: Rotational atherectomy with adjunctive balloon angioplasty has satisfactory technical success rates and mid-term outcomes. As an adjunctive method, there was no difference between drug-coated balloon angioplasty s and POBAs. Smoking cessation is always the first-step treatment to improve mid-term patency results. Patients with critical limb ischemia have worse patency results compared to the patients with claudication.

A systematic review and meta-analysis of gender differences in long-term mortality and cardiovascular events in peripheral artery disease.

OBJECTIVE: Individual studies of peripheral artery disease (PAD) have indicated that gender discrepancies exist in the symptoms, functional status, and treatment usage. It remains uncertain whether these discrepancies result in different long-term outcomes. We examined the potential gender differences in mortality and major adverse cardiovascular events (MACE) in patients with symptomatic PAD. METHODS: The PubMed and Embase databases were searched for studies from 2000 to January 2019. After a review of 13,582 citations, 14 articles were analyzed. The reported age-adjusted hazard ratios (HRs) for gender differences in mortality and MACE were included in the meta-analysis. The mortality outcomes were stratified according to the clinical presentation and study context. RESULTS: Male gender was associated with a greater risk of all-cause mortality (HR, 1.13; 95% confidence interval [CI], 1.10-1.16; P < .001) and MACE (HR, 1.10; 95% CI, 1.06-1.14; P < .001). In a stratified analysis, male gender was associated with a higher mortality risk for patients presenting with either critical limb ischemia (HR, 1.08; 95% CI, 1.05-1.10; P < .001) or mixed clinical presentations (HR, 1.16; 95% CI, 1.11-1.21; P < .001) but not for those with intermittent claudication (HR, 1.13; 95% CI, 0.98-1.30; P = .09). Elevated mortality risk was evident after revascularization (HR, 1.11; 95% CI, 1.04-1.19; P = .003), hospitalization (HR, 1.15; 95% CI, 1.08-1.22; P < .001), and amputation (HR, 1.09; 95% CI, 1.08-1.10; P < .001), although not in outpatient clinics (HR, 1.13; 95% CI, 0.97-1.32; P = .13), in men compared with women. CONCLUSIONS: Greater mortality and MACE rates in men with PAD occurred despite other accepted gender disparities. The mechanisms underlying these gender differences in the outcomes for PAD patients require further investigation.

Discrepancy in Outcomes after Revascularization for Chronic Limb-Threatening Ischemia Warrants Separate Reporting of Rest Pain and Tissue Loss.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) manifests as rest pain (RP) and tissue loss (TL). Outcomes of lower extremity revascularization (LER) for CLTI have traditionally been evaluated as a single entity and compared with claudication. We hypothesize that patients presenting with TL have worse short-term outcomes after LER, compared to patients with RP. METHODS: The National Inpatient Sample was reviewed between 2009 and 2013. All patients undergoing LER for TL and RP were identified. Patient characteristics, Charlson Comorbidity Index (CCI), length of stay, rates of inpatient major amputation, and mortality after LER were noted. Multivariable regression analysis was performed to identify predictors of inpatient mortality and major amputation between the 2 groups. RESULTS: A total of 218,628 patients underwent LER (RP = 76,108, TL = 142,519). Patients with TL were more likely to undergo endovascular LER (RP = 31.3% vs. TL = 48.7%; P < 0.001). Patients with TL had higher comorbidities as suggested by increased likelihood of having CCI ≥3 (RP = 22.9% vs. TL = 40.3%; P < 0.001). The mean costs were significantly higher in the TL group (RP = $23,795 vs. TL = $31,470; P < 0.001). There was a significantly higher rate of major amputation (RP = 1.3% vs. TL = 6.6%; P < 0.001) and inpatient mortality (RP = 0.9% vs. TL = 1.9%; P < 0.001) after LER for TL. On multivariable analysis, TL was independently associated with increased major amputation (odds ratio [OR] 4.93, 95% confidence interval [CI] 4.18-5.81) and increased mortality (OR 1.42, 95% CI 1.16-1.74) compared to RP. CONCLUSIONS: There is significant discrepancy in outcomes of LER for TL and RP. TL is independently associated with major amputation and inpatient mortality. Outcomes of LER for TL and RP should be reported separately for better benchmarking.

Tibial bypass in patients with intermittent claudication is associated with poor outcomes.

OBJECTIVE: Given that intermittent claudication (IC) rarely progresses to chronic limb-threatening ischemia and limb loss, safety and durability of elective interventions for IC are essential. Whether patients with IC benefit from tibial intervention is controversial, and data supporting its utility are limited. Despite endovascular therapy expansion, surgical bypass is still commonly performed. We sought to assess outcomes of bypass to tibial arteries for IC. METHODS: The Vascular Quality Initiative (2003-2018) was queried for infrainguinal bypasses performed for IC. Perioperative and 1-year outcomes were compared between bypasses constructed to tibial and popliteal arteries. RESULTS: Of 5347 infrainguinal bypasses, 1173 (22%) and 4184 (78%) were tibial and popliteal bypasses, respectively. Overall, mean age was 65 ± 10 years, and patients were often men (72%) and current smokers (42%). Tibial bypasses commonly targeted posterior tibial (40%), tibioperoneal trunk (23%), and anterior tibial (19%) arteries. Great saphenous vein was more often used for tibial bypass than for popliteal bypass (78% vs 54%; P < .001). Patients undergoing tibial compared with popliteal bypass more often had impaired ambulation and prior ipsilateral bypasses and were less often taking antiplatelets and statins (all P < .05). In the perioperative period, tibial bypass patients had longer postoperative length of stay (4.5 ± 3.5 vs 3.5 ± 2.8 days), more pulmonary complications (1.3% vs 0.6%), and higher return to the operating room (7% vs 4%; all P < .05). Perioperative myocardial infarction (1.2% vs 0.8%; P = .19), stroke (0.4% vs 0.4%; P = .91), and mortality (0.3 vs 0.3%; P = .86) rates were similar between the cohorts. At 1 year, tibial compared with popliteal bypasses exhibited lower freedom from occlusion/death (81% vs 89%; P < .001), ipsilateral major amputation/death (90% vs 94%; P < .001), and reintervention/amputation/death (73% vs 80%; P < .001), but patient survival was similar (96% vs 97%; P = .07). On multivariable analysis, tibial compared with popliteal bypass was independently associated with increased occlusion/death (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.28-2.11; P < .001), major ipsilateral amputation/death (HR, 1.6; 95% CI, 1.12-2.19; P = .003), and ipsilateral reintervention/amputation/death (HR, 1.51; 95% CI, 1.28-1.79; P < .001), with similar patient survival. CONCLUSIONS: In patients with IC, tibial bypass was associated with poor outcomes, including major amputation. Surgeons should exhaust nonoperative therapies and present realistic outcome expectations to their patients before offering such intervention.

Registry Assessment of Peripheral Interventional Devices objective performance goals for superficial femoral and popliteal artery peripheral vascular interventions.

BACKGROUND: The Superficial Femoral Artery-Popliteal EvidencE Development Study Group developed contemporary objective performance goals (OPGs) for peripheral vascular interventions (PVI) for superficial femoral artery (SFA)-popliteal artery disease using the Registry Assessment of Peripheral Interventional Devices. METHODS: The Society for Vascular Surgery Vascular Quality Initiative PVI registry from January 2010 to October 2016 was used to develop OPGs based on SFA-popliteal procedures (n = 21,377) for intermittent claudication and critical limb ischemia (CLI). OPGs included 1-year rates for target lesion revascularization (TLR), major amputation, and 1 and 4-year survival rates. OPGs were calculated for the SFA and popliteal arteries and stratified by four treatments: angioplasty alone (percutaneous transluminal angioplasty [PTA]), self-expanding stenting, atherectomy, and any treatment type. Outcomes were illustrated by unadjusted Kaplan-Meier analyses. RESULTS: Cohorts included PTA (n = 7505), stenting (n = 9217), atherectomy (n = 2510) and any treatment (n = 21,377). The mean age was 69 years, 58% were male, 79% were White, and 52% had CLI. The freedom from TLR OPGs at 1 year in the SFA were 80.3% (PTA), 83.2% (stenting), 83.9% (atherectomy), and 81.9% (any treatments). The freedom from TLR OPGs at 1 year in the popliteal were 81.3% (PTA), 81.3% (stenting), 80.2% (atherectomy), and 81.1% (any treatments). The freedom from major amputation OPGs at 1 year after SFA PVI were 93.4% (PTA), 95.7% (stenting), 95.1% (atherectomy), and 94.8% (any treatments). The freedom from major amputation OPG at 1 year after popliteal PVI were 90.5% (PTA), 93.7% (stenting), 91.8% (atherectomy), and 91.8%, (any treatments). The 4-year survival OPGs after SFA PVI were 76% (PTA), 80% (stenting), 82% (atherectomy), and 79% (any treatments), and for the popliteal artery were 72% (PTA), 77% (stenting), 82% (atherectomy), and 75% (any treatment). On a multivariable analysis, which included patient-level, leg-level, and lesion-level covariates, CLI was the single independent factor associated with increased TLR, amputation, and mortality. CONCLUSIONS: The Superficial Femoral Artery-Popliteal EvidencE Development OPGs define a new, contemporary benchmark for SFA-popliteal interventions using a large subset of real-world evidence to inform more efficient peripheral device clinical trial designs to support regulatory and clinical decision-making. It is appropriate to discuss proposals intended for regulatory approval with the US Food and Drug Administration to refine the OPG to match the specific trial population. The OPGs may be updated using coordinated registry networks to assess long-term real-world device performance.

Modified frailty index as an indicator for outcomes, discharge status, and readmission after lower extremity bypass surgery for critical limb ischemia.

Frailty has been associated with poor postoperative outcomes. This study evaluated the 5-factor modified frailty index (mFI-5) to assess complications, mortality, discharge disposition, and readmission in patients undergoing lower extremity (LE) bypass for critical limb ischemia (CLI).The National Surgical Quality Improvement Program vascular module (2011-2017) was utilized to identify patients undergoing LE bypass for CLI. Adverse events included infectious complications, bleeding complications, prolonged ventilation, amputation, readmission, and death. Patients were divided into groups based on mFI-5 scores: mFI1 (0), mFI2 (0.2), mFI3 (0.4), and mFI4 (0.6-1). Data were analyzed using the Cochran-Mantel-Haenszel statistic for general association and multivariable logistic regression. About 11,530 patients undergoing bypass for CLI were identified (42% rest pain and 58% tissue loss; 23% mFI1, 31% mFI2, 27% mFI3, and 19% mFI4; 64% men and 36% women). An increase in mFI-5 was associated with higher 30-day mortality (mFI1 = 0.62%; mFI12 = 1.45%; mFI13 = 1.35%; and mFI14 = 3.09%; P < .0001). After adjustment for age, mFI4 was associated with increased mortality compared with mFI1 (odds ratio, 3.80; 95% confidence interval, 1.69-8.54). Increased mFI-5 was associated with bleeding complications, wound infections, urinary tract infections, prolonged ventilation, sepsis, unplanned reoperations, and discharge to nonhome destination (all P < .01). Compared with mFI1 (13.5%), mFI4 was associated with increased 30-day readmission (24.8%, P < .0001). In patients undergoing LE bypass for CLI, higher mFI-5 was associated with increased postoperative complications, in-hospital and 30-day mortality, nonhome discharge, and 30-day readmission. The mFI-5 as an easily calculated tool can identify patients at high risk for inferior outcomes. It should be incorporated into discharge planning after LE bypass for CLI.

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

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

Three-Year Outcomes of Orbital Atherectomy for the Endovascular Treatment of Infrainguinal Claudication or Chronic Limb-Threatening Ischemia.

Purpose: To investigate the outcomes of orbital atherectomy (OA) for the treatment of patients with peripheral artery disease (PAD) manifesting as claudication or chronic limb-threatening ischemia (CLTI). Materials and Methods: The database from the LIBERTY study (ClinicalTrials.gov identifier NCT01855412) was interrogated to identify 503 PAD patients treated with any commercially available endovascular devices and adjunctive OA for 617 femoropopliteal and/or infrapopliteal lesions. Cox regression analyses were employed to examine the association between baseline Rutherford category (RC) stratified as RC 2-3 (n=214), RC 4-5 (n=233), or RC 6 (n=56) and all-cause mortality, target vessel revascularization (TVR), major amputation, major adverse event (MAE), and major amputation/death at up to 3 years of follow-up. The mean lesion lengths were 78.7±73.7, 131.4±119.0, and 95.2±83.9 mm, respectively, for the 3 groups. Results: After OA, balloon angioplasty was used in >98% of cases, with bailout stenting necessary in 2.0%, 2.8%, and 0% of the RC groups, respectively. A small proportion (10.8%) of patients developed angiographic complications, without differences based on presentation. During the 3-year follow-up, claudicants were at lower risk for MAE, death, and major amputation/death than patients with CLTI. The 3-year Kaplan-Meier survival estimates were 84.6% for the RC 2-3 group, 76.2% for the RC 4-5 group, and 63.7% for the RC 6 group. The 3-year freedom from major amputation was estimated as 100%, 95.3%, and 88.6%, respectively. Among CLTI patients only, the RC at baseline was correlated with the combined outcome of major amputation/death, whereas RC classification did not affect TVR, MAE, major amputation, or death rates. Conclusion: Peripheral artery angioplasty with adjunctive OA in patients with CLTI or claudication is safe and associated with low major amputation rates after 3 years of follow-up. These results demonstrate the utility of OA for patients across the spectrum of PAD.

Impact of Kidney Disease on Peripheral Arterial Interventions: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited data on outcomes of patients undergoing peripheral arterial disease (PAD) interventions who have comorbid CKD/ESRD versus those who do not have such comorbid condition. We performed a systematic review and meta-analysis to analyze outcomes in this patient population. METHODS: Five databases were searched for studies comparing outcomes of lower extremity PAD interventions for claudication and critical limb ischemia (CLI) in patients with CKD/ESRD versus non-CKD/non-ESRD from January 2000 to June 2019. RESULTS: Our study included 16 observational studies with 44,138 patients. Mean follow-up was 48.9 ± 27.4 months. Major amputation was higher with CKD/ESRD compared with non-CKD/non-ESRD (odds ratio [OR 1.97] [95% confidence interval [CI] 1.39-2.80], p = 0.001). Higher major amputations with CKD/ESRD versus non-CKD/non-ESRD were only observed when indication for procedure was CLI (OR 2.27 [95% CI 1.53-3.36], p < 0.0001) but were similar for claudication (OR 1.15 [95% CI 0.53-2.49], p = 0.72). The risk of early mortality was high with CKD/ESRD patients undergoing PAD interventions compared with non-CKD/non-ESRD (OR 2.55 [95% CI 1.65-3.96], p < 0.0001), which when stratified based on indication, remained higher with CLI (OR 3.14 [95% CI 1.80-5.48], p < 0.0001) but was similar with claudication (OR 1.83 [95% CI 0.90-3.72], p = 0.1). Funnel plot of included studies showed moderate bias. CONCLUSIONS: Patients undergoing lower extremity PAD interventions for CLI who also have comorbid CKD/ESRD have an increased risk of experiencing major amputations and early mortality. Randomized trials to understand outcomes of PAD interventions in this at-risk population are essential.

Impact of Institutional Volume on Critical In-Hospital Complications Adjusted for Patient- and Limb-Related Characteristics: An Analysis of a Nationwide Japanese Registry of Endovascular Interventions for PAD.

PURPOSE: To investigate the incidence and clinical predictors, including institutional annual case volume, of critical in-hospital complications after endovascular therapy (EVT) for peripheral artery disease (PAD). MATERIALS AND METHODS: The data were extracted from the nationwide registry of peripheral interventions in Japan [Japanese EVT (J-EVT)] between 2012 and 2017. A total of 92,224 EVT cases either for chronic limb-threatening ischemia (CLTI) or intermittent claudication were included in the analysis. The primary outcome measure was critical in-hospital complications, which were defined as a composite of urgent surgery and in-hospital death within 30 days after EVT. The institutional volume was classified into quartiles. The association of institutional volume, as well as baseline characteristics, with the critical in-hospital complications was explored using a multivariable logistic regression model with multiple imputation for missing data. Results are presented as the adjusted odds ratio (OR) with the 95% confidence intervals (CI). RESULTS: The estimated prevalence of critical in-hospital complications was 0.3% (95% CI 0.3% to 0.4%). The following 10 patient- and limb-related characteristics were identified as independent risk factors for critical in-hospital complications: (1) female sex (OR 1.75, 95% CI 1.36 to 2.25), (2) age ≥75 years (OR 1.60, 95% CI 1.06 to 2.40), (3) CLTI (OR 2.12, 95% CI 1.47 to 3.05), (4) nonambulatory status (OR 1.66, 95% CI 1.23 to 2.24), (5) regular dialysis (OR 1.35, 95% CI 1.02 to 1.77), (6) cerebrovascular disease (OR 1.76, 95% CI 1.33 to 2.33), (7) urgent revascularization (OR 5.10, 95% CI 3.64 to 7.13), (8) aortoiliac TASC II D lesion (OR 3.65, 95% CI 2.51 to 5.33), (9) femoropopliteal TASC II D lesion (OR 1.77, 95% CI 1.24 to 2.52), and (10) infrapopliteal TASC D lesion (OR 1.52, 95% CI 1.08 to 2.13). In addition, the 4th quartile of the institutional volume (≥158 cases/year), but not the 2nd or 3rd quartile, had a significantly and independently lower risk of critical in-hospital complications than the 1st quartile (OR 0.13, 95% CI 0.07 to 0.23). CONCLUSION: After EVT for symptomatic PAD, 0.3% of the population encountered critical in-hospital complications. A higher institutional volume was significantly associated with a lower risk of critical in-hospital complications.