Peripheral Artery Disease Outcomes Research Articles

Alginate-Encapsulated Mesenchymal Stromal Cells Improve Hind Limb Ischemia in a Translational Swine Model.

Cellular therapies have been investigated to improve blood flow and prevent amputation in peripheral artery disease with limited efficacy in clinical trials. Alginate-encapsulated mesenchymal stromal cells (eMSCs) demonstrated improved retention and survival and promoted vascular generation in murine hind limb ischemia through their secretome, but large animal evaluation is necessary for human applicability. We sought to determine the efficacy of eMSCs for peripheral artery disease-induced limb ischemia through assessment in our durable swine hind limb ischemia model. Autologous bone marrow eMSCs or empty alginate capsules were intramuscularly injected 2 weeks post-hind limb ischemia establishment (N=4/group). Improvements were quantified for 4 weeks through walkway gait analysis, contrast angiography, blood pressures, fluorescent microsphere perfusion, and muscle morphology and histology. Capsules remained intact with mesenchymal stromal cells retained for 4 weeks. Adenosine-induced perfusion deficits and muscle atrophy in ischemic limbs were significantly improved by eMSCs versus empty capsules (mean±SD, 1.07±0.19 versus 0.41±0.16, P=0.002 for perfusion ratios and 2.79±0.12 versus 1.90±0.62 g/kg, P=0.029 for ischemic muscle mass). Force- and temporal-associated walkway parameters normalized (ratio, 0.63±0.35 at week 3 versus 1.02±0.19 preligation; P=0.17), and compensatory footfall patterning was diminished in eMSC-administered swine (12.58±8.46% versus 34.85±15.26%; P=0.043). Delivery of eMSCs was associated with trending benefits in collateralization, local neovascularization, and muscle fibrosis. Hypoxia-cultured porcine mesenchymal stromal cells secreted vascular endothelial growth factor and tissue inhibitor of metalloproteinase 2. This study demonstrates the promise of the mesenchymal stromal cell secretome at improving peripheral artery disease outcomes and the potential for this novel swine model to serve as a component of the preclinical pipeline for advanced therapies.

The Impact of Mental Health on Patient Outcomes in Peripheral Arterial Disease and Critical Limb Threatening Ischemia and Potential Avenues to Treatment

The physical consequences of peripheral arterial disease (PAD) are well established, however, the impact of comorbid mental health disorders such as depression and anxiety are not well understood. The impact of psychological stress is not only associated with worse perioperative morbidity and mortality but also with a physiologic cascade that accelerates plaque formation. Increasing screening to identify and subsequently treat comorbid mental health disorders is an integral next step in improving outcomes in PAD management. Failure to adequately address social and psychological impact on PAD patients will further widen the gap in disparities faced by high risk and disenfranchised populations. Integration of mental health professionals, addiction specialists, and community navigators into multidisciplinary care teams can bolster support for PAD patients and improve outcomes.

Reconsidering the Impact of Endovascular Repair on Short-Term and Mid-Term Outcomes in Peripheral Arterial Disease: A Retrospective Analysis

ObjectiveThe aim of the study is to compare the short and medium-term outcomes in patients who underwent open repair (OR) or endovascular repair (ER) for peripheral arterial disease (PAD) also including stratifications based on severity and year of the first intervention. DesignObservational retrospective single-center cohort study. MethodsWe evaluated patients with PAD that primarily underwent ER, OR, minor and major amputations in a single center from 2005 to 2020. The patients were then subdivided according to the type of intervention (OR vs ER), and stratified according to the ICD-9 code reported in the operating documents and to the year intervention. Mortality, minor and major amputation rates occurring at 30 days, 2 and 5 years after the first intervention were evaluated as primary outcomes and compared between patient groups in both stratifications. Moreover, Kaplan-Maier (KM) curves were analyzed for these outcomes. Results1492 patients (67.0% males) with PAD were evaluated. Their clinical presentations were intermittent claudication in 51.4% of cases, rest pain in 16.8%, ulcers in 10.3%, and gangrene in 21.5%. 997 (66.8%) underwent OR and 495 (33.2%) ER as first intervention for PAD. No statistical differences were observed in terms of mortality in the two groups (OR vs ER, p=1.000, p=0.357, p=0.688 at 30 days, 2 and 5 years respectively). The rate of minor amputations was significantly higher (p<.012, p<.002, p<.007 at 30 days, 2 and 5 years respectively) for ER group in any of the observed follow-up periods. Also, we have observed that OR and ER do not have any significant short- and medium-term major amputation rate differences. ConclusionIn our experience, the impact of ER does not significantly change short- and mid-term major outcomes in patients with PAD.

Outcomes of peripheral artery disease and polyvascular disease in patients with end-stage kidney disease

ObjectivePatients with peripheral artery disease (PAD) and end-stage kidney disease are a high-risk population, and concomitant atherosclerosis in coronary arteries (CAD) or cerebral arteries (CVD) is common. The aim of the study was to assess long-term outcomes of PAD and the impact of coexistent CAD and CVD on outcomes. MethodsThe United States Renal Data System was used to identify patients with PAD within 6 months of incident dialysis. Four groups were formed: PAD alone, PAD with CAD, PAD with CVD, and PAD with CAD and CVD. PAD-specific outcomes (chronic limb-threatening ischemia, major amputation, percutaneous/surgical revascularization, and their composite, defined as major adverse limb events [MALE]) as well as all-cause mortality, myocardial infarction, and stroke were studied. ResultsThe study included 106,567 patients (mean age, 71.2 years; 40.8% female) with a median follow-up of 546 days (interquartile range, 214-1096 days). Most patients had PAD and CAD (49.8%), 25.8% had PAD alone, and 19.2% had all three territories involved. MALE rate in patients with PAD was 22.3% and 35.0% at 1 and 3 years, respectively. In comparison to PAD alone, the coexistence of both CAD and CVD (ie, polyvascular disease) was associated with a higher adjusted rates of all-cause mortality (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.24-1.31), myocardial infarction (HR, 1.78; 95% CI, 1.69-1.88), stroke (HR, 1.66; 95% CI, 1.52,1.80), and MALE (HR, 1.07; 95% CI, 1.04-1.11). ConclusionsPatients with end-stage kidney disease have a high burden of PAD with poor long-term outcomes, which worsen, in an incremental fashion, with the involvement of each additional diseased arterial bed.

Clinical Utility of Infrapopliteal Calcium Score for the Evaluation of Severity of Peripheral Artery Disease

PurposeTo identify associations between computed tomography (CT)–based lower-extremity calcium score (LECS) across different anatomic segments and the presence, severity, and clinical outcomes of peripheral artery disease (PAD). Materials and MethodsIn a mixed retrospective and prospective cohort study, 139 patients without prior lower-extremity intervention who underwent CT angiography of the aorta and lower extremities were identified. Subjects were classified as asymptomatic, claudicants, or having chronic limb-threatening ischemia (CLTI). LECS was measured using the Agatston method. Univariate and multivariate analyses were performed across categories of PAD severity. Receiver operating characteristic (ROC) analysis was performed, and an optimal cutoff point for LECS was identified. Claudicants were followed prospectively for CLTI and mortality. ResultsHigher infrapopliteal calcium score (CS) was independently associated with CLTI versus claudication (odds ratio [OR], 3.24 per unit increase in log10-transformed CS; P < .001) in addition to hemodialysis dependence and poor functional status. One hundred eighty-eight Agatston units was identified as the optimal cutoff for infrapopliteal CS in assessing the risk of CLTI versus claudication (area under the ROC curve, 0.84 [SD ± 0.049]). This cutoff was validated in an independent cohort to be associated with progression to CLTI (OR, 12.8; P = .0039). In the claudicant group followed prospectively, infrapopliteal CS ≥188 predicted increased risk of CLTI or death after adjusting for functional status and hemodialysis dependence (Cox hazard ratio, 4.92; P = .0202). ConclusionsHigher infrapopliteal CS was associated with CLTI among those with symptomatic PAD. An infrapopliteal CS cutoff of 188 Agatston units may serve as a useful tool to identify patients with increased risk of CLTI and mortality.

TCT-282 Outcomes of Peripheral Artery Disease in Octogenarians, Nonagenarians, and Centenarians: A Retrospective Cohort Study

TCT-282 Outcomes of Peripheral Artery Disease in Octogenarians, Nonagenarians, and Centenarians: A Retrospective Cohort Study

Stem Cell Therapy in Critical Limb Ischemia.

Critical limb ischemia (CLI), a serious outcome of peripheral artery disease, is frequently associated with morbid outcomes. The available treatment modalities do not provide satisfactory results, leading to marked morbidities such as joint contracture and amputations, resulting in a high economic burden. The peripheral vascular disease tends to cause more morbidity in patients with diabetes and atherosclerosis, given the pre-existing compromised perfusion of medium and small vessels in diabetic patients. With surgical procedures, the chance of vascular compromise further increases, inducing a significantly greater rate of amputation. Hence, the need for nonsurgical treatment modalities such as stem cell therapy (SCT), which promotes angiogenesis, is warranted. In CLI, SCT acts through neovascularization and the development of collateral arteries, which increases blood supply to the soft tissues of the ischemic limb, providing satisfactory outcomes. An electronic database search was performed in PubMed, SCOPUS, EMBASE, and ScienceDirect to identify published clinical trial data, research studies, and review articles on stem cell therapy in critical limb ischemia. The search resulted in a total of 2391 results. Duplicate articles screening resulted in 565 articles. In-depth screening of abstracts and research titles excluded 520 articles, yielding 45 articles suitable for full-text review. On review of full text, articles with overlapping and similar results were filtered, ending in 25 articles. SCT promotes arteriogenesis, and bone marrow-derived mesenchymal stromal cells produce significant effects like reduced morbidity, improved amputation-free survival (AFS ) rate, and improved distal perfusion even in "no-option" CLI patients. SCT is a promising treatment modality for CLI patients, even in those in whom endovascular and revascularization procedures are impossible. SCT assures a prolonged AFS rate, improved distal perfusion, improved walking distances, reduced amputation rates, and increased survival ratio, and is well-tolerated.

Cohort Study Examining the Presentation, Distribution, and Outcomes of Peripheral Artery Disease in Aboriginal, Torres Strait Islander, and Non-Indigenous Australians

This retrospective cohort study investigated the anatomical distribution, severity, and outcome of peripheral artery disease (PAD) in Aboriginal and Torres Strait Islander compared with non-Indigenous Australians. The distribution, severity, and outcome of PAD were assessed using a validated angiographic scoring system and review of medical records in a cohort of Aboriginal and Torres Strait Islander and non-Indigenous Australians. The relationship between ethnicity and PAD severity, distribution, and outcome were examined using non-parametric statistical tests, Kaplan-Meier and Cox proportional hazard analyses. Seventy-three Aboriginal and Torres Strait Islander and 242 non-Indigenous Australians were included and followed for a median of 6.7 [IQR 2.7, 9.3] years. Aboriginal and Torres Strait Islander patients were more likely to present with symptoms of chronic limb threatening ischaemia (81% vs. 25%; p < .001), had greater median [IQR] angiographic scores for the symptomatic limb (7 [5, 10] vs. 4 [2, 7]) and tibial arteries (5 [2, 6] vs. 2 [0, 4]) and had higher risk of major amputation (HR 6.1, 95% CI 3.6 - 10.5; p < .001) and major adverse cardiovascular events (HR 1.5, 95% CI 1.0 - 2.3; p = .036) but not for revascularisation (HR 0.8, 95% CI 0.5 - 1.3; p = .37) compared with non-Indigenous Australians. The associations with major amputation and major adverse cardiovascular events were no longer statistically significant when adjusted for limb angiographic score. Compared with non-Indigenous patients, Aboriginal and Torres Strait Islander Australians had more severe tibial artery disease and higher risk of major amputation and major adverse cardiovascular events.

Association between complete revascularization of the coronary artery and clinical outcomes in peripheral artery disease: a sub-analysis of the I-PAD Nagano registry

Peripheral artery disease (PAD) is commonly caused by atherosclerosis and has an unfavorable prognosis. Complete revascularization (CR) of the coronary artery reduces the risk of major adverse cardiovascular event (MACE) in patients with coronary artery disease (CAD). However, the impact of CR in patients with PAD has not been established to date. Therefore, we evaluated the impact of CR of CAD on the five-year clinical outcomes in patients with PAD. This study was based on a prospective, multicenter, observational registry in Japan. We enrolled 366 patients with PAD undergoing endovascular treatment. The primary endpoint was MACE, defined as a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke. After excluding ineligible patients, 96 and 68 patients received complete revascularization of the coronary artery (CR group) and incomplete revascularization of the coronary artery (ICR group), respectively. Freedom from MACE in the CR group was significantly higher than in the ICR group at 5 years (66.7% vs 46.0%, p < 0.01). Multivariate analysis revealed that CR emerged as an independent predictor of MACE (Hazard ratio: 0.56, 95% confidential interval: 0.34–0.94, p = 0.03). CR of CAD was significantly associated with improved clinical outcomes in patients with PAD undergoing endovascular treatment.

The Relationship Between Peripheral Arterial Disease Severity and Socioeconomic Status

Although socioeconomic disparities in outcomes of peripheral arterial disease (PAD) have been well studied, little is known about relationship between severity of PAD and socioeconomic status. The objective of this study was to examine this relationship. Patients who had operations for severe PAD (rest pain or tissue loss) were identified in the National Inpatient Sample, 2005 - 2014. They were stratified by the median household income (MHI) quartiles of their residential ZIP codes. Other characteristics such as race/ethnicity and insurance type were extracted. Factors associated with more severe disease (tissue loss) were evaluated using multivariable regression analyses. There were 765,175 patients identified; 34% in the 1st MHI quartile and 18% in the 4th MHI quartile. Compared to patients in the 1st quartile, those in the 4th quartile were more likely White (69% vs. 42%, P <0.001), more likely ≥65 years old (75% vs. 62%, P <0.001), and were less likely to undergo amputations (25% vs. 34%, P <0.001). After adjusting for patient characteristics, the 4th quartile was associated with more severe disease [Odds ratio: 1.19, 95% CI: 1.11 - 1.27] compared to the 1st quartile.. While higher MHI was associated with higher PAD severity, patients with high MHI were less likely to undergo amputations indicating a disparity in the choice of treatment for PAD. Increased efforts are necessary to reduce socioeconomic disparities in the treatment of severe PAD.

Smoking cessation for peripheral arterial disease: systematic review protocol.

peripheral arterial disease has smoking as its main avoidable vascular risk factor. However, most studies do not focus on smoking as the main exposure variable. to assess the impact of smoking cessation interventions versus active comparator, placebo or no intervention, on peripheral arterial disease outcomes. we will use the Cochrane Handbook for Systematic Reviews of Interventions to guide whole this review process. We will consider parallel or cluster-randomised controlled trials (RCTs), quasi-RCTs, and cohort studies. We will search CENTRAL, MEDLINE, Embase, PsycINFO, LILACS and IBECS. We will also conduct a search of ClinicalTrials.gov and the ICTRP for ongoing or unpublished trials. Each research step will involve at least two independent reviewers. We will create a table, using GRADE pro GDT software, reporting the pooled effect estimates for the following outcomes: all-cause mortality, lower limb amputation, adverse events, walking distance, clinical severity, vessel or graft secondary patency, and QoL. we will assess these outcomes according to the five GRADE considerations to assess the certainty of the body of evidence for these outcomes, and to draw conclusions about the certainty of the evidence within the review.

Attendance at Supervised Exercise Sessions and Walking Outcomes in Peripheral Artery Disease: Results From 2 Randomized Clinical Trials.

Background Supervised exercise therapy (SET) is the first-line therapy for walking impairment in peripheral artery disease (PAD). This study evaluated the association between attendance at SET and improved walking performance, compared with a control group, in PAD. Methods and Results Data from 2 randomized clinical trials of SET for PAD were combined. In each trial, participants were randomized to 3 times weekly supervised treadmill exercise or an attention control group for 6 months (maximum, 77 exercise sessions). Participants randomized to SET were categorized into tertiles, according to the proportion of exercise sessions they attended. Results adjusted for age, sex, race, baseline walking performance, comorbidities, and other potential confounders. A total of 272 participants with PAD (mean age, 67.9±9.3 years; 44% women; 61% Black race) were included. For participants randomized to SET, tertiles of attendance rates at exercise sessions were as follows: 11% to 68% (N=45), 69% to <85% (N=46), and ≥85% (N=46). Compared with control, mean improvement in 6-minute walk was significantly greater in each SET tertile: mean (95% CI) for tertile 1, 27.9 m (1.3-54.4 m; P=0.04), tertile 2, 38.2 m (12.2-64.2 m; P=0.001), and tertile 3, 56.9 m (29.9-83.8 m; P<0.0001). Among participants randomized to SET, greater SET attendance was associated with greater improvement in 6-minute walk distance (overall P for trend=0.025). Compared with control, improvement in maximal treadmill walking time was greater in each SET attendance tertile: tertile 1 (3.3 minutes [95% CI, 1.7-4.8 minutes]; P<0.0001), tertile 2 (3.8 minutes [95% CI, 2.3-5.3 minutes]; P<0.0001), and tertile 3 (5.4 minutes [95% CI, 3.9-7.0 minutes]; P:<0.0001). Among participants randomized to SET, greater attendance at SET was not significantly associated with greater improvement in maximal treadmill walking time (overall P for trend=0.064). Conclusions Among people with PAD randomized to SET, better attendance at exercise sessions was associated with significantly greater 6-minute walk improvement. Among all participants with PAD, even relatively low SET attendance was associated with significantly greater improvement in walking performance, compared with a control group who did not exercise. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01408901. URL: https://clinicaltrials.gov/ct2/show/NCT00106327.

Comparison of Angiographic Characteristics of Peripheral Arterial Disease between Diabetic and Non-Diabetics

Background and Aim: Several factors contribute to the poor outcomes of peripheral arterial disease (PAD). The current study examined the results of peripheral transluminal angioplasty (PTA) in diabetics and non-diabetics with peripheral arterial disease (PAD). Patients and Methods: This cross-sectional study was carried out on 136 peripheral arteries disease patients including 84 non-diabetic and 52 diabetics in the department of Cardiology, Hayatabad Medical Complex, Peshawar during the period from January 2022 to June 2022. This study included patients with PADs who had PTAs performed on their femoral, iliac, infrapopliteal, and popliteal arteries. Study protocol was approved by the research and ethical committee. Patient’s demographic details and medical history were recorded. SPSS version 26 was used for data analysis. Results: The overall mean age was 64.6 ± 10.51 years. Diabetic patients were compared with non-diabetic patients in terms of age (63.8±11.2 versus 65.4± 9.82 years), smoking history (80.7% vs. 46.4%), hypercholesterolemia (25.4% versus 31.9%), and ischemic heart disease (40.6% versus 36.5%). The frequency of hypertensive patients was higher 64.8% in diabetic patients against 40.6% in non-diabetic patients. In terms of arterial segment below the knee and profunda femoris, arterial disease had higher severity in diabetic patients. Diabetic patients were more susceptible to amputation (43.2% vs. 12%, OR=4.8, P=0.001) and had higher mortality (48.9% versus 23.8%). Conclusion: The present study found that higher prevalence of limb ischemia, amputation, and higher rates of restenosis following peripheral transluminal angioplasty was found in diabetic patients compared to non-diabetic patients. Diabetic patients had poor prognosis and worse arterial disease than non-diabetic patients. Keywords: Diabetic patients, Angiographic characteristics, Peripheral arteries disease.

Prevalence and outcomes of peripheral artery disease in a real-world cohort of patients with acute coronary syndrome: insights from the prospective SPUM registry

Abstract Background Despite substantial improvement in secondary preventive therapy, the burden of recurrent cardiovascular (CV) events remains high. Peripheral artery disease (PAD), is a potential marker of increased residual ischemic risk in acute coronary syndrome (ACS) patients suggesting greater net clinical benefit from intensified individualized therapy. Purpose We aimed to assess the prevalence and cardiovascular (CV) outcomes of peripheral arterial disease (PAD) in 4'787 patients with acute coronary syndromes (ACS) in the Swiss prospective multicenter SPUM study. Methods PAD was defined according to international guidelines. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), i.e., stroke, myocardial infarction (MI) and death at 1 year. Adjusted Cox proportional hazards regression models were used to estimate the risk associated with PAD and outcomes. Results Out of 4'787 ACS patients, 285 patients (6.0%) had PAD. These patients were older (70.1±10.6 vs 63.3±12.4, p&amp;lt;0.001), presented all traditional CV risk factors (all p&amp;lt;0.001) and were more likely to have a complex history of CV disease, such as previous MI (24.3% vs 11.4%, p&amp;lt;0.001), prior percutaneous (32.3% vs 13.8%, p&amp;lt;0.001) or surgical (12.6% vs 3.5%, p&amp;lt;0.001) coronary revascularization. PAD-patients presented also higher levels of inflammatory biomarkers, such as hs-CRP, and GRACE 2.0 score (all p&amp;lt;0.001). At 1 year, patients with PAD had a higher rate of MACCE compared to those presenting without PAD. Rates of the individual components of the primary endpoint and CV-death were all significantly higher in patients with PAD (all p&amp;lt;0.001), except for a numerical increase in MI (5.3% vs 3.3%, p=0.060). This enhanced risk persisted after adjustment for differences in baseline characteristics, with a 53% (Adj. HR 1.53, CI95% 1.14–2.08, p=0.005) increase in MACCE. In spite of high-intensity anti-thrombotic therapy, PAD patients presented the same rate (Adj. HR 1.03, CI95% 0.68–1.54, p=0.901) of major bleeding events at 1 year. Conclusions Among a real-world cohort of ACS patients, the coexistence of PAD, a very-high CV risk phenotype, is associated with significantly increased rates of MACCE, but no difference in major bleeding events. These observations might help clinicians to further stratify this very-high risk population and to identify patients who may derive the greatest benefit from more intense secondary prevention therapies. Funding Acknowledgement Type of funding sources: None.

Comorbid Depression is Associated with Increased Major Adverse Limb Events in Peripheral Arterial Disease: A Systematic Review and Meta-analysis

Depression is a significant risk factor for death in coronary artery disease. Conversely, the research surrounding depression and peripheral arterial disease is limited. This review aimed to systematically evaluate the available literature on the impact of comorbid depression on adverse outcomes in peripheral arterial disease.

Understanding Study Drug Discontinuation Through EUCLID

IntroductionDisparities in the care and outcomes of peripheral artery disease (PAD) have been well-established. In part this is due to disparities in enrollment of PAD trial cohorts. However, less attention has been paid to non-random protocol non-adherence after enrollment, which may lead to inaccurate estimates of treatment effects and reduce generalizability of study results. We aimed to ascertain characteristics associated with premature study drug discontinuation in a PAD cohort.MethodsUsing data from EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease), factors associated with study drug discontinuation were assessed using univariable and multivariable Cox proportional hazards models with time to study drug discontinuation as the outcome of interest. Relationships between study drug discontinuation and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, ischemic stroke), major adverse limb events (MALE; acute limb ischemia, major amputation, and lower extremity revascularization), and all-cause hospitalization were assessed.ResultsOf 13,842 eligible EUCLID participants, 3,886 (28.1%) prematurely and permanently discontinued study drug over a maximum follow-up of 42 months (annualized rate of 13.2 discontinuations per 100 patient-years). In a multivariable model, premature study drug discontinuation was associated with older age (aHR 1.16, 95%CI 1.14–1.19), eligibility based on prior lower extremity revascularization rather than ABI/TBI criteria (aHR 1.14, 95%CI 1.06–1.23), CLI status (aHR 1.23, 95%CI 1.06–1.42), COPD (aHR 1.36, 95%CI 1.24–1.49), and geographic region. In a multivariable analysis, study drug discontinuation was significantly associated with MACE (aHR 3.27, 95%CI 2.90–3.67, p < 0.001), MALE (aHR 1.84, 95%CI 1.63–2.07, p < 0.001), and all-cause hospitalization (aHR 2.37, 95%CI 2.21–2.54) following study drug discontinuation.ConclusionsThis analysis of EUCLID demonstrates that premature, permanent discontinuation of study drug is relatively common in more than a quarter of PAD patients, is unevenly distributed based on geography and other baseline characteristics, and is associated with worse outcomes in a clinical trial context. Study teams leading future PAD trials may want to address the possibility of study drug discontinuation prospectively, as a proactive approach may help investigators to maintain study cohort diversity and representativeness without sacrificing power and precision.

Prognostic impact of atrial fibrillation on the outcomes of peripheral artery disease according to preoperative symptoms for endovascular revascularization.

Peripheral artery disease (PAD) and atrial fibrillation (AF) are associated with major cardiovascular and cerebrovascular events (MACCE). However, outcomes stratified according to the preoperative symptoms of PAD in patients with AF have not been sufficiently investigated. This was a retrospective study of prospectively collected data pertaining to 2237 patients (1179 patients with intermittent claudication [IC] and 1058 patients with critical limb-threatening ischemia [CLTI]) who underwent endovascular therapy at 34 hospitals between August 2014 and August 2016. AF was present in 91 (7.7%) patients with IC and 150 (14.2%) patients with CLTI. In the CLTI group, patients with AF had a higher event rate of MACCE and all-cause death than those without AF (1-year rates of freedom from MACCE: 0.66 and 0.81 in patients with and without AF, respectively, p < 0.001). In contrast, in the IC group, there was no statistically significant difference in the rates of MACCE between patients with and without AF. In the Cox multivariate analysis, AF was a significant predictor of MACCE in patients with CLTI but not in patients with IC, even after adjusting for covariates. The impact of AF on the outcome of patients with PAD was greater in those with CLTI. Further studies are needed to clarify the possible mechanisms underlying these differences.

Clinical non-effectiveness of clopidogrel use for peripheral artery disease in patients with CYP2C19 polymorphisms: a systematic review.

To conduct a systematic review to identify studies that assessed the association between CYP2C19 polymorphisms and clinical outcomes in peripheral artery disease (PAD) patients who took clopidogrel. We systematically searched Ovid EMBASE, PubMed, and Web of Science from November 1997 (inception) to September 2020. We included observational studies evaluating how CYP2C19 polymorphism is associated with clopidogrel's effectiveness and safety among patients with PAD. We extracted relevant information details from eligible studies (e.g., study type, patient population, study outcomes). We used the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) Tool to assess the risk of bias for included observational studies. The outcomes of interest were the effectiveness and safety of clopidogrel. The effectiveness outcomes included clinical ineffectiveness (e.g., restenosis). The safety outcomes included bleeding and death related to the use of clopidogrel. We identified four observational studies with a sample size ranging from 50 to 278. Outcomes and comparison groups of the studies varied. Three studies (75%) had an overall low risk of bias. All included studies demonstrated that carrying CYP2C19 loss of function (LOF) alleles was significantly associated with reduced clinical effectiveness and safety of clopidogrel. Our systematic review showed an association between CYP2C19 LOF alleles and reduced functions of clopidogrel. The use of CYP2C19 testing in PAD patients prescribed clopidogrel may help improve the clinical outcomes. However, based on the limited evidence, there is a need for randomized clinical trials in PAD patients to test both the effectiveness and safety outcomes of clopidogrel.

A systematic review of racial/ethnic disparities in pharmacotherapy and surgical treatment outcomes in peripheral arterial disease among African American/non-Hispanic Black, non-Hispanic White and Hispanic patients

BackgroundLower extremity peripheral arterial disease (PAD) is associated with significant morbidity and mortality in racial/ethnic diverse populations. However, limited data exist on treatment outcome disparities in racial/ethnic diverse populations, particularly in AA/NHB populations. ObjectiveThe aim of this systematic review is to analyze disparities in the outcomes of PAD treatments, particularly pharmacotherapy and surgery, among racial/ethnic groups in the US. MethodsA comprehensive search of original investigations pertaining to PAD treatments between 2015 and 2021 was performed. Quality assessment of the studies was also completed. ResultsFourteen studies were included. Thirteen studies reported differences in treatment outcomes for surgical intervention, and one study reported differences for concurrent surgical and pharmacotherapy. NHB and Hispanic/Latinx ethnicities were associated with decreased overall and perioperative mortality in four studies. Six studies noted increased amputation risk among racial/ethnic diverse populations. Only one study noted significant survival benefit by race/ethnicity. Three studies noted increased risk of major adverse limb events and post-operative complications. One study noted increased limb patency after intervention in racial/ethnic cohorts. Overall, all studies reported high methodological quality with adequate assessment of outcomes and follow-up of cohort. ConclusionIn this analysis, the predominant intervention reported is surgical. Overall, racial/ethnic populations are less likely to experience PAD-associated mortality but are more likely to experience adverse events. Further studies are necessary to include all racial/ethnic diverse populations in assessing PAD therapeutic intervention outcomes. Moreover, targeted public health efforts are necessary to increase PAD educational awareness, community-driven risk modification, and patient-centered care planning.

The effect of lifestyle and risk factor modification on occlusive peripheral arterial disease outcomes: standard healthcare vs structured programme: a pilot randomised controlled study

Abstract Funding Acknowledgements Type of funding sources: None. Background Atherosclerotic risk factor modification plays an important role in reducing adverse outcomes in patients with atherosclerotic disease1. Despite the high prevalence of peripheral arterial disease (PAD) and strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive structured treatment for their atherosclerotic risk factors than patients with coronary artery disease2,3. Purpose We aim to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors. Methods This is a pilot randomised controlled study comparing a risk factor modification intervention programme to standard healthcare, for the reduction of modified risk factors in PAD patients. Patients randomised to the intervention arm underwent a 12-week supervised programme adjusting their risk factors. Primary outcome was patients reaching target risk factor improvement. Results Seventy-five patients were randomised. 36 were allocated to Standard Healthcare. 39 completed a 12-week Structured Programme. There was no significant difference between groups in baseline demographics, incidence and severity of risk factors, mobility and quality of life. At 12-weeks the intervention group showed a significant improvement in target body weight (6.7±9.57 p=0.002), waist circumference (7.4±9.5 p=0.001), HbA1c (4.12±7.22 p=0.009), total cholesterol (0.63±0.99 p=0.004), low-density lipoprotein (0.59±1.040 p=0.00), triglycerides (0.24±0.38 p=0.005), Mediterranean diet score (2.48±1.35 p=0.0001), Absolute Walking Distance (8.2±7.8 p=0.0001), Claudication Distance (9.2±7.4 p=0.0001). There was no significant difference in the change of any of the other risk factors. Conclusion Risk factor modification intervention programme can significantly aid PAD patients reach their target risk factor improvement goals.