Lower Extremity Arterial Disease Research Articles

2024 Guideline for Management of Wounds in Patients With Lower Extremity Arterial Disease: An Executive Summary.

This article is an executive summary of the Wound, Ostomy, and Continence Nurses Society's (WOCN) 2024 Guideline for Management of Wounds in Patients With Lower Extremity Arterial Disease. It is part of the Society's Clinical Practice Guideline Series. This article presents an overview of the systematic process used to update and develop the guideline. It also lists specific recommendations from the guideline for screening and diagnosis, assessment, management, and education of patients with wounds due to lower extremity arterial disease (LEAD). Suggestions for implementing recommendations from the guideline are also summarized. The guideline is a resource for WOC nurse specialists, other nurses, and health care professionals who work with adults who have/or are at risk of wounds due to LEAD. The complete guideline includes the evidence and references supporting the recommendations, and it is available from the WOCN Society's Bookstore (www.wocn.org). Refer to the Supplemental Digital Content Appendix (available at: http://links.lww.com/JWOCN/A123) associated with this article for a complete reference list for the guideline.

Application opportunity of Doppler ultrasound combined with CT angiography in diabetic lower extremity arterial disease and the analysis of the risk factors.

This study examined the potential of combining Doppler ultrasound (DUS) and CT angiography (CTA) for early detection and intervention of lower extremity arterial disease (LEAD) in diabetes.Concurrently, risk factors influencing LEAD progression were analyzed. 106 Type-2 diabetes patients with LEAD, having undergone DUS and CTA, were divided into four stages according to Fontaine stage. Results of DUS and CTA were compared across stages and potential risk factors were analyzed. Positive detection rates of LEAD differed between DUS and CTA for Fontaine stages I and II (P < 0.05), with no significant difference for stages III and IV (P > 0.05). CTA identified subgroups with mild to moderate stenosis and severe stenosis or occlusion, with positive rates on DUS of 17.95% and 89.9% respectively. Hypertension was found as an independent risk factor affecting LEAD progression. CTA should be performed early for LEAD in diabetes patients at Fontaine stages I and II, regardless of DUS results. For diabetes patients with LEAD, stringent blood pressure control is crucial to delay disease progression.

Impact of a Less Than 50% Residual Stenosis Following Vessel Preparation in Femoropopliteal Drug-Coated Balloon Angioplasty.

Drug-coated balloon (DCB) has been established as first-line therapy in femoropopliteal (FP) intervention, and successful vessel preparation (VP) is considered a key element. However, the clinical impact of successful VP remains unknown. This retrospective study examined the clinical impact of successful VP in DCB FP intervention. In total, 268 patients (308 limbs) who underwent successful FP intervention using DCB without atherectomy devices for symptomatic lower extremity artery disease between March 2018 and December 2019 were included in this study (high-dose DCB: 69.8%; low-dose DCB: 30.2%). Successful VP was defined as <50% residual stenosis and <dissection grade D before DCB (the successful VP group). The primary outcome measure was primary patency, and its associated factors were evaluated. The median follow-up period was 2.1 (interquartile range=1.1-2.7) years. Successful VP was achieved in 163 patients (60.8%). Primary patency and freedom from clinically-driven target lesion revascularization (CD-TLR) were significantly higher in the successful VP group than in the nonsuccessful VP group (54.2% vs 33.0%, p<0.001; 69.9% vs 57.7%, p=0.047). In the successful VP group, high-dose DCB and low-dose DCB were comparable in primary patency and freedom from CD-TLR (53.2% vs 53.6%, p=0.48; 68.7% vs 70.9%, p=0.69). In nonsuccessful VP group, high-dose DCB demonstrated numerically higher primary patency but not statistically significant than low-dose DCB (44.5% vs 16.0%, p=0.06), whereas no significant difference in freedom from CD-TLR was observed (56.0% vs 58.9%, p=0.29). On multivariate analysis, successful VP and preballoon size to reference vessel diameter ratio were significantly associated with primary patency. Achieving successful VP before DCB was independently associated with primary patency in DCB FP intervention. This study revealed that the successful vessel preparation (VP) before DCB and preballoonsize to reference vessel diameter ratio were independently associated with primary patency in DCB femoropopliteal intervention. When successful VP was achieved only before DCB treatment, the clinical outcomes were comparable between high-dose DCB and low-dose DCB at midterm follow-up.To maximized DCB efficacy, successful VP is very important in daily clinical practice.

The role of the adenylate kinase 5 gene in various diseases and cancer

Abstract Adenylate kinases (AKs) are important enzymes involved in cellular energy metabolism. Among AKs, AK5 (adenylate kinase 5), a cytosolic protein, is emerging as a significant contributor to various diseases and cellular processes. This comprehensive review integrates findings from various research groups on AK5 since its discovery, shedding light on its multifaceted roles in nucleotide metabolism, energy regulation, and cellular differentiation. We investigate its implications in a spectrum of diseases, including autoimmune encephalitis, epilepsy, neurodegenerative disorders such as Alzheimer’s and Parkinson’s, diabetes, lower extremity arterial disease, celiac disease, and various cancers. Notably, AK5’s expression levels and methylation status have been associated with cancer progression and patient outcomes, indicating its potential as a prognostic indicator. Furthermore, AK5 is implicated in regulating cellular processes in breast cancer, gastric cancer, colorectal carcinoma, prostate cancer, and colon adenocarcinoma, suggesting its relevance across different cancer types. However, a limitation lies in the need for more robust clinical validation and a deeper understanding of AK5’s precise mechanisms in disease pathogenesis, despite its association with various pathophysiological conditions. Nonetheless, AK5 holds promise as a therapeutic target, with emerging evidence suggesting its potential in therapy development.

Lower Extremity Arterial Disease in Patients with Type 2 Diabetes: Prevalence and Associated Factors at the Libreville University Hospital Center

Lower Extremity Arterial Disease in Patients with Type 2 Diabetes: Prevalence and Associated Factors at the Libreville University Hospital Center

Fibroblast Growth Factors in Cardiovascular Disease.

Despite advancements in managing traditional cardiovascular risk factors, many cardiovascular diseases (CVDs) persist. Fibroblast growth factors (FGFs) have emerged as potential diagnostic markers and therapeutic targets for CVDs. FGF1, FGF2, and FGF4 are primarily used for therapeutic angiogenesis. Clinical applications are being explored based on animal studies using approaches such as recombinant protein administration and adenovirus-mediated gene delivery, targeting patients with coronary artery disease and lower extremity arterial disease. Although promising results have been observed in animal models and early-stage clinical trials, further studies are required to assess their therapeutic potential. The FGF19 subfamily, consisting of FGF19, FGF21, and FGF23, act via endocrine signaling in various organs. FGF19, primarily expressed in the small intestine, plays important roles in glucose, lipid, and bile acid metabolism and has therapeutic potential for metabolic disorders. FGF21, found in various tissues, improves glucose metabolism and insulin sensitivity, suggesting potential for treating obesity and diabetes. FGF23, primarily secreted by osteocytes, regulates vitamin D and phosphate metabolism and serves as an important biomarker for chronic kidney disease and CVDs. Thus, FGFs holds promise for both therapeutic and diagnostic applications in metabolic and cardiovascular diseases. Understanding the mechanisms of FGF may pave the way for novel strategies to prevent and manage CVDs, potentially addressing the limitations of current treatments. This review explores the roles of FGF1, FGF2, FGF4, and the FGF19 subfamily in maintaining cardiovascular health. Further research and clinical trials are crucial to fully understand the therapeutic potential of FGFs in managing cardiovascular health.

Growth Differentiation Factor-15 and Clinical Outcomes in Lower Extremity Artery Disease.

Lower extremity artery disease (LEAD) is an increasingly common health problem that is associated with high mortality due to thrombotic and bleeding events. Growth differentiation factor-15 (GDF15), a stress-response cytokine belonging to the transforming growth factor-beta superfamily, is associated with cardiovascular disease and its outcomes. The aim of the present study was to examine the effect of serum GDF15 levels on clinical outcomes in patients with LEAD. We measured serum GDF15 levels in 200 patients with LEAD before their initial endovascular therapy. The primary endpoint was the all-cause mortality rate. The secondary endpoints, on the other hand, were thrombotic and bleeding events, such as cerebral infarction, acute coronary syndrome, acute limb ischemia, and Bleeding Academic Research Consortium types 3 and 5. The serum GDF15 levels increased with advancing Fontaine class. Kaplan-Meier analysis revealed that the high-GDF15 group (≥ 2,275 pg/mL) had higher rates of all-cause deaths and thrombotic and bleeding events than the low-GDF15 group (＜2,275 pg/mL). Multivariate Cox proportional-hazards regression analysis revealed that GDF15 was an independent predictor of all-cause mortality and thrombotic and bleeding events after adjusting for confounding risk factors. When the ABC-AF-bleeding score was substituted for GDF15, similar results were obtained. Serum GDF15 levels were associated with all-cause mortality and thrombotic and bleeding events in patients with LEAD. Serum GDF15 is a potentially useful marker of clinical outcomes, specifically for tracking thrombotic and bleeding events in patients with LEAD.

Microbiological Distribution, Antimicrobial Susceptibility and Risk Factors of Polymicrobial Infections in Diabetic Foot.

Diabetic foot infection (DFI) leads to poor prognosis and polymicrobial infections are usually the main cause. The study is to explore the microbiological distribution, antimicrobial drug susceptibility, and risk factors of polymicrobial infections in hospitalized patients with DFI. This retrospective study included 160 patients with DFI in Wagner's grades 2, 3, and 4. Deep necrotic tissue was used to acquire specimens for microbiological culture. VITEK-2 system and MALDI-TOF mass spectrometry were used to identify the bacterial isolates. The Kirby Bauer method was used for drug susceptibility tests. A total of 202 pathogens were isolated. The proportion of gram-negative bacilli (GNB, 62.4%, 126 of 202) was higher than that of gram-positive cocci (GPC, 37.6%, 76 of 202). The most prevalent GPC was Staphylococcus aureus in every Wagner grade, while the most common GNB varied in different Wagner grades. Linezolid was the most effective antibiotic for GPC in different Wagner grades. Imipenem was the most effective antibiotic for GNB in Wagner grade 2. Amikacin was the most effective antibiotic for GNB in Wagner grades 3 and 4. Polymicrobial infections existed only in Wagner grades 3 and 4 and increased the risk of amputation (p < 0.01). History of antibiotics, duration of diabetic foot, CRP, and lower extremity arterial disease were the independent risk factors of polymicrobial infections (p < 0.05). Clinicians should adjust the antibiotic as needed based on the results of drug susceptibility and clinical treatment effect among different Wagner grades. Particular attention should be given to the treatment of polymicrobial infections.

Intravascular ultrasound use in peripheral arterial and deep venous interventions: Multidisciplinary expert opinion from SCAI/AVF/AVLS/SIR/SVM/SVS

Percutaneous revascularization is the primary strategy for treating lower extremity venous and arterial disease. Angiography is limited by its ability to accurately size vessels, precisely determine the degree of stenosis and length of lesions, characterize lesion morphology, or correctly diagnose postintervention complications. These limitations are overcome with use of intravascular ultrasound (IVUS). IVUS has demonstrated the ability to improve outcomes following percutaneous coronary intervention, and there is increasing evidence to support its benefits in the setting of peripheral vascular intervention. At this stage in its evolution, there remains a need to standardize the use and approach to peripheral vascular IVUS imaging. This manuscript represents considerations and consensus perspectives that emerged from a roundtable discussion including 15 physicians with expertise in interventional cardiology, interventional radiology, and vascular surgery, representing 6 cardiovascular specialty societies, held on February 3, 2023. The roundtable’s aims were to assess the current state of lower extremity revascularization, identify knowledge gaps and need for evidence, and determine how IVUS can improve care and outcomes for patients with peripheral arterial and deep venous pathology.

The efficacy and safety of atherectomy combined with drug-coated balloon angioplasty vs. drug-coated balloon angioplasty for the treatment of lower extremity artery disease: a systematic review and meta-analysis.

This study aimed to systematically evaluate the efficacy and safety of atherectomy followed by drug-coated balloon angioplasty (A-DCB) in comparison with drug-coated balloon (DCB) angioplasty alone for the treatment of lower extremity artery disease (LEAD). Systematic literature search was performed using several online databases including MEDLINE (via PubMed), Europe PMC, and ScienceDirect databases from inception until February 21st, 2024. We included all studies comprised three main variables including A-DCB, DCB, and LEAD. The primary outcomes were primary patency and target lesion revascularization (TLR). Whereas secondary outcomes were all-cause mortality, post-procedural complications, and clinical characteristics. A total of 15 studies (10 cohort studies and 5 randomized controlled trials studies) consisting of 1,385 participants with mean age 68.7 ± 8.9 were included. In comparison with DCB alone, A-DCB was significantly associated with a higher risk of primary patency [RR = 1.16 (95% CI = 1.07-1.26); P < 0.001; I 2 = 20.9%, P-heterogeneity = 0.221] and lower risk of TLR [RR = 0.61 (95% CI = 0.46-0.81); P < 0.001; I 2 = 0%, P-heterogeneity = 0.475]. Subgroup analysis showed that only directional, rotational, and laser atherectomy increased the probability of primary patency, but only rotational atherectomy decreased the risk of TLR. Regarding secondary outcomes, A-DCB was substantially associated with a lower likelihood of bailout stenting, any amputation, and major amputation, as well as higher ankle brachial index (ABI) following follow-up duration. Meta-regression analysis suggested that pre-intervention s (p = 0.015) and pre-intervention Rutherford classification (p = 0.038) were significantly affected the association between A-DCB and primary patency. Begg's funnel plot and Egger's test analyses indicated no publication bias in this meta-analysis. The addition of atherectomy improves primary patency and reduces the risk of TLR with similar safety outcomes. www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382831, PROSPERO (CRD42022382831).

Nationwide study in France to predict one-year major bleeding and validate the OAC3-PAD score in patients undergoing revascularisation for lower extremity arterial disease

Nationwide study in France to predict one-year major bleeding and validate the OAC3-PAD score in patients undergoing revascularisation for lower extremity arterial disease

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study

Background and AimsPrimary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD).MethodsWe included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship.ResultsIn whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03–1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27–3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10–2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08–1.34]) for LEAD, 1.48 [95% CI 1.28–1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy.ConclusionsPrimary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Implementation of holistic nursing interventions based on fast track surgery concept in patients with lower extremity arterial occlusive disease.

Lower Extremity Arterial Occlusive Disease (LEAOD) is a prevalent condition affecting many patients worldwide, which requires careful management and patient cooperation. This study aimed to evaluate the effectiveness of holistic nursing interventions based on the Fast Track Surgery (FTS) concept in patients with LEAOD. A retrospective analysis of 92 LEAOD patients, randomized into control and experimental groups, was performed. Conventional rehabilitation nursing interventions were applied to the control group, while the experimental group received holistic rehabilitation nursing interventions based on the FTS concept. Patient adherence was assessed before and after the intervention using a hospital survey, and sleep quality was evaluated using the Pittsburgh Sleep Quality Index on days 3, 7, and 15 post-interventions. Post-intervention, the experimental group exhibited significantly improved adherence to balanced diet, regular exercise, timely medication, and regular review visits compared to the control group (P < .05). Further, Pittsburgh Sleep Quality Index scores indicated significantly better sleep quality over time in the experimental group than in the control group (P < .05). The implementation of holistic nursing interventions based on the FTS concept significantly improved patient adherence and sleep quality in LEAOD patients. These findings highlight the potential benefits of integrating such interventions in the management of LEAOD patients, potentially enhancing postoperative recovery and overall health outcomes.

Bypass failure of internal mammary artery caused by subclavian artery stenosis: its clinical characteristics and cardiovascular outcomes in patients receiving coronary artery bypass graft surgery.

While internal mammary artery (IMA) has become a major conduit of coronary artery bypass graft (CABG) surgery, subclavian artery stenosis (SAS) could cause subsequent coronary events due to ischemia of myocardial territory supplied by IMA. Clinical characteristics and cardiovascular outcomes of SAS-related IMA failure (SAS-IMAF) remain to be fully determined yet. Therefore, the current study was designed to characterize SAS-IMAF in patients receiving CABG with IMA. This is a retrospective observational study which analyzed 380 patients who presented acute coronary syndrome/stable ischemic heart disease (ACS/SIHD) after CABG using IMA (2005.01.01-2020.10.31). SAS-IMAF was defined as the presence of myocardial ischemia/necrosis caused by SAS. Clinical characteristics and cardiovascular outcomes [major adverse cardiovascular events (MACE) = cardiac death + non-fatal myocardial infarction + non-fatal ischemic stroke], were compared in subjects with and without SAS-IMAF. Multivariate Cox proportional hazards model and propensity score-matched analyses were used to compare cardiovascular outcomes between those with and without SAS-IMAF. SAS-IMAF was identified in 5.5% (21/380) of study subjects. Patients with SAS-IMAF are more likely had a history of hemodialysis (P<0.001), stroke (P<0.001) and lower extremity artery disease (P<0.001). Furthermore, SAS-IMAF patients more frequently presented ACS (P=0.002) and required mechanical support (P=0.02). Despite SAS as a culprit lesion causing ACS/SIHD, percutaneous coronary intervention was firstly selected in 47.6% (10/21) of them. Consequently, 33.3% (7/21) of SAS-IMAF patients required additional revascularization procedure (vs. 0.3%, P<0.001). During 4.9-year observational period, SAS-IMAF exhibited a 5.82-fold [95% confidence interval (CI): 2.31-14.65, P<0.001] increased risk of MACE. Multivariate Cox proportional hazards model [hazard ratio (HR) 4.04, 95% CI: 1.44-11.38, P=0.008] and propensity score-matched analyses (HR 2.67, 95% CI: 1.06-6.73, P=0.038) consistently demonstrated the association of SAS-IMAF with MACE. SAS-IMAF reflects a high-risk phenotype of polyvascular disease, underscoring meticulous evaluation of subclavian artery after CABG using IMA.

Outcomes of non-flow-limiting spiral dissection after drug-coated balloon angioplasty for de novo femoropopliteal lesions.

Whether drug-coated balloon (DCB) angioplasty would be effective in spiral dissection (SD) lesions with no flow impairment has been thoroughly investigated. The present study sought to assess the clinical outcomes of non-flow-limiting SD after DCB angioplasty for de novo femoropopliteal lesions in patients with symptomatic lower extremity artery disease. This single-center retrospective study enrolled 497 patients with non-flow-limiting SD (n = 92) or non-SD (n = 405) without bailout stenting. The primary endpoint was 1-year primary patency, with the secondary endpoints including freedom from target lesion revascularization (TLR), major adverse limb event (MALE), all-cause death, and 30-day restenosis. The 1-year primary patency and freedom from TLR were significantly lower in the SD group than in the non-SD group (69.8% vs. 83.3%, p = 0.004; 78.7% vs. 93.0%, p = 0.007, respectively). The SD group had a higher incidence of MALE and 30-day restenosis than the non-SD group (24.6% vs. 11.9%, p = 0.001; 4.3% vs. 0.5%, p = 0.002, respectively). All-cause death was comparable. One-year restenosis after SD was associated with chronic limb-threatening ischemia (CLTI) (hazard ratio, 3.36 [95% confidence interval, 1.21-9.36]; p = 0.020), TASC Ⅱ D (hazard ratio, 3.97 [95% confidence interval, 1.02-15.52]; p = 0.047), and residual stenosis ≥50% (hazard ratio, 4.92 [95% confidence interval, 1.01-23.94]; p = 0.048). The incidence of restenosis after SD increased with the number of these risk factors. Despite normal antegrade flow, the 1-year primary patency rate after DCB angioplasty for de novo femoropopliteal lesions was significantly lower in lesions with SD than those without SD. CLTI, TASC II D, and residual stenosis ≥50% were risk factors associated with 1-year restenosis after DCB angioplasty for non-flow-limiting SD lesions.

Usefulness of a novel nutritional index associated with frailty and poor outcomes in patients with lower extremity arterial disease

Abstract Background Evidence has indicated the close association between malnutrition or frailty and adverse outcomes in patients with lower extremity arterial disease (LEAD) following endovascular treatment (EVT). We have previously proposed a novel and simply calculable nutritional index by using serum levels of triglyceride, total cholesterol and body weight (TCBI) which was a useful prognostic indicator for patients with several cardiovascular disorders such as coronary artery disease, cardiogenic shock and heart failure. However, the application of the TCBI in patients with LEAD has been rarely evaluated. Moreover, no study has simultaneously addressed the prognostic implication of nutritional and frailty indices. Purpose The aim of present study was to investigate the association between TCBI and an index of frailty and sarcopenia, computed tomography (CT)-based psoas muscle index (PMI), in patients with LEAD following EVT. Moreover, we assessed the prognostic implication of TCBI in this population. Methods This single-center retrospective analysis involved consecutive patients with LEAD who underwent EVT for the first time since 2009 to 2020 (n=591). We divided patients into three groups according to tertiles of TCBI: lowest tertile (T1, &amp;lt;731.1); middle tertile (T2, 731.1–1243.6); and highest tertile (T3, ≥1243.6). We measured cross-sectional areas of psoas muscle at the level of forth lumber vertebra by CT-scan and obtained PMI (psoas muscle area normalized by height) in study participants. Primary and secondary endpoints were all-cause death and major adverse cardiovascular and limb events (MACLE), the composite of cardiovascular death (CV death), non-fatal myocardial infarction, stroke, clinically driven target vessel revascularization (CD-TVR), major amputation and development to limb ischemia. Median and the range of follow up period was 2.3 and 0–10 years, respectively. Results There was a positive significant correlation between log-transformed TCBI and PMI (Spearman’s correlation coefficient (r) between TCBI and PMI: 0.31, p&amp;lt;0.0001) (Figure 1). Kaplan-Meier analyses revealed the lowest cumulative incidences of both all-cause death and MACLE in patients with the highest tertile of TCBI (Figure 2). Constantly, multivariate Cox hazard analyses adjusted by age, sex, prior myocardial infarction, diabetes, chronic kidney disease (≥ stage3), left ventricular ejection fraction, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and serum albumin level indicated the decreased risk of all-cause death (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.44–0.91, p=0.02) and MACLE (HR: 0.73, 95% CI: 0.59–0.89, p=0.003) by increase of TCBI, respectively. Conclusion This study showed a potential pathological link between poor nutritional status and advanced frailty/sarcopenia, which was associated with increased risk of poor prognosis in patients with LEAD following EVT.

Dual pathway inhibitor therapy switched from dual antiplatelet therapy reduces risk of recurrent in-stent occlusion after endovascular therapy for femoropopliteal in-stent occlusion

Abstract Background Femoropopliteal (FP) in-stent occlusion (ISO), which increases the risk of repetition of reintervention and worsens the limb prognosis, is substantially encountered in clinical setting.1,2 Although previous study demonstrated that dual pathway inhibitor therapy (DPIT) reduced major adverse cardiovascular and limb events, whether this would be effective as anti-thrombotic therapy after endovascular therapy (EVT) for FP-ISO.3 Purpose To investigate whether DPIT reduces a risk of recurrent ISO after EVT for FP-ISO. Methods We retrospectively studied 117 limbs (chronic limb-threatening ischemia: 52%, chronic total occlusion: 74%) in 110 symptomatic patients with lower extremity arterial disease (male: 55%, diabetes mellitus: 49%) due to FP-ISO between August 2012 and October 2021. We compared the clinical outcomes of patients who were switched from dual antiplatelet therapy (DAPT) to DPIT with those who continued DAPT (DPIT group: 25 limbs in 25 patients, DAPT group: 92 limbs in 85 patients) after FP-ISO revascularization. The outcome measures were recurrent ISO and bleeding complications defined as the bleeding academic research criteria (BARC) and the International Society on Thrombosis and Haemostasis (ISTH). Cox proportional hazards regression models were used to identify prognostic factor of recurrent ISO. Results The 1-year cumulative incidence of recurrent ISO was significantly lower in DPIT group. (24.0±9.4% vs. 54.1±5.8%, p=0.037, Figure 1). The 1-year cumulative incidence of bleeding complications were similar between two groups (BRAC 3 or 5 bleeding: 4.2% vs. 2.4%, p=0.63), ISTH major bleeding: 12.6% vs. 11.4%, p=0.86) (Figure 2). Multivariate analysis revealed that DPIT group (hazard ratio [HR]: 0.34, 95% confidential interval [CI] 0.13-0.86, P=0.004) significantly associated with a reduced risk of recurrent ISO, whereas higher age (HR: 1.05, 95%CI 1.01-1.09, P=0.006) and poor BTK run-off (HR: 4.77, 95%CI 1.76-12.91, P=0.002) were significantly associated with an increased risk. Conclusion Switching from DAPT to DPIT after EVT for FP-ISO reduced the risk of recurrent ISO without increasing the risk of bleeding, while higher age and poor BTK run-off increased the risk of recurrent ISO.Figure 1Figure 2

Design of knowledge-based mechanistic model of atherosclerotic cardiovascular disease for in silico trials

Abstract In silico trials applying a computational model (CM) of atherosclerotic cardiovascular disease (ASCVD) to virtual patients receiving alternative treatments provide an attractive option to complement randomised clinical trials (RCTs) by adding comparative effectiveness data and facilitating the demonstration of drug benefit. In silico modelling allows comparison between treatments with each virtual patient being his own control, and is not limited by the number of patients, comparative arms or trial duration. This study aims at building a knowledge-based mechanistic model of ASCVD. Once validated, the model will be used to run in silico clinical trials to compare the benefit of inclisiran, an siRNA targeting PCSK9 mRNA, vs other lipid-lowering therapies (LLT) on cardiovascular (CV) events in patients with ASCVD. An extensive literature review was performed to identify pathophysiological mechanisms involved in ASCVD and therapeutic mechanisms of action (MOAs). Every piece of knowledge extracted from the literature is awarded a strength of evidence grading to allow tracking of uncertainty in the model. A panel of multidisciplinary experts reviewed knowledge models and subsequent modelling hypotheses to validate their relevance. Knowledge was translated into mathematical equations. Each functional relationship between entities is represented by a biochemical/biophysical reaction with its reaction rate. A system of ordinary differential equations provides dynamics of modelled biological entities. A strategy of model calibration/validation was defined with the expert panel, by selecting relevant RCT and registry data, that the model should be able to reproduce. A virtual population was generated to account for inter-patient variability. A mechanistic CM of ASCVD (including 72 biological entities, 750 parameters) was built from knowledge, describing lipoproteins metabolism and cholesterol homeostasis, dynamics of atherosclerotic plaque growth with lipoproteins infiltration in the intima and evolution of lipidic, necrotic and fibrotic tissues as well as plaque rupture leading to myocardial infarction, ischemic stroke, lower extremity arterial disease or CV death. It also includes the impact of several risk factors (age, sex medical history, diabetes, hypertension, smoking, systemic inflammation, chronic kidney disease) and available LLT (atorvastatin, rosuvastatin, ezetimibe, evolocumab and inclisiran). After calibration, the model and virtual population reproduce pharmacokinetics of LLT, lipoproteins decrease under combinations of LLT and associated reduction in clinical events. ASCVD is ideally suited for in silico modelling: extensive literature is available regarding the pathophysiology, therapeutic MOAs are known and easily integrated in the model, clinically relevant outcomes are adequate model outputs, RCT and registry data exist to calibrate/validate the model. The next step is validation of the model before using it to run in silico trials.Plaque growth and rupture modelMulti-scale in silico model

Rivaroxaban plus aspirin vs. dual antiplatelet therapy in endovascular treatment in peripheral artery disease and analysis of medication utilization of different lesioned vascular regions.

In the management of Peripheral Arterial Disease (PAD), the administration of anticoagulant or antiplatelet agents is imperative. The use of Dual Antiplatelet Therapy (DAPT) in conjunction with rivaroxaban has shown potential in mitigating adverse outcomes. Given the heterogeneity in the pathology of lower limb arteries, there is a compelling case for individualized treatment strategies. In a single-center retrospective study on pharmacotherapy for peripheral artery disease, patients were treated with either aspirin combined with rivaroxaban or aspirin coupled with clopidogrel. The primary efficacy outcome encompassed a composite of increases in the Rutherford classification, acute limb ischemia, amputations due to vascular causes, target lesion revascularization, myocardial infarction, ischemic stroke, and cardiovascular death. The primary safety outcome was major bleeding, as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria; meanwhile, major bleeding as categorized by the International Society on Thrombosis and Haemostasis (ISTH) served as a secondary safety outcome. The study differentiated between two subgroups: patients with only above-the-knee and below-the-knee arterial lesions. From January 2016 to December 2021, 455 patients received either clopidogrel plus aspirin or rivaroxaban plus aspirin following endovascular treatment (EVT). The rivaroxaban group (n = 220) exhibited a lower incidence of primary efficacy outcomes [49.1% vs. 60.4%, hazard ratio (HR) 0.77, P = 0.006] but had more TIMI major bleeding events (5.9% vs. 2.1%, HR 2.6, P = 0.04). ISTH major bleeding events did not show a significant difference, though a higher percentage of rivaroxaban patients discontinued medication due to bleeding (10% vs. 4.7%, HR 2.2, P = 0.03). In the above-the-knee arterial disease subgroup, the rivaroxaban group demonstrated a lower incidence of primary efficacy outcomes (28.2% vs. 45.2%, HR 0.55, P = 0.02). In the below-the-knee arterial disease subgroup, no significant difference was observed in the occurrence of primary efficacy events between the two groups (58.7% vs. 64.8%, HR 0.76, P = 0.14). Rivaroxaban plus aspirin improved outcomes compared to DAPT in patients with lower extremity artery disease. Similar findings were observed in the above-the-knee artery lesion-only group. However, in the below-the-knee artery lesion-only group, rivaroxaban plus aspirin did not surpass DAPT in efficacy. Regarding safety, rivaroxaban plus aspirin exhibited higher bleeding risks and more frequent treatment discontinuation than aspirin combined with clopidogrel.

Long-term prognostic risk score for CLTI including nutritional state

Abstract Background Chronic limb-threatening ischemia (CLTI) is well known for its poor prognosis. Although nutritional state is reportedly related to outcome, few studies have considered a long-term prognostic score for CLTI that includes nutritional status. Methods The I-PAD registry was a prospective, multicenter, observational patient registry designed to provide up to 5 years of clinical follow-up data. A total of 366 patients having undergone 463 endovascular treatments for symptomatic lower extremity artery disease were enrolled, from which 125 patients with CLTI were analyzed. We searched for prognostic predictors including nutritional status for amputation-free survival (AFS) to develop a scoring system for long-term CLTI prognosis. Results Median patient age was 77 [68, 86] years and follow-up period was 1729 [797, 1954] days. Cox multivariate analysis revealed Geriatric Nutritional Risk Index score &amp;lt;92 points, &amp;gt;71 years of age, female, heart failure, and anemia (&amp;lt;13.0 g/dL in men and &amp;lt;12.0 g/dL in women) to be significant prognostic predictors for AFS (all p&amp;lt;0.05). We calculated the weighted risk score for each prognostic factor (0 to 11 points) and divided the cohort into the high score group (≥4 points) and low score group (≤3 points). The incidence of AFS at 5 years was significantly lower in the high score group (35.4% vs. 89.5%, p&amp;lt;0.001). The area under the receiver operating characteristic curve was 0.81 for 5-year AFS. Conclusion A higher prognostic score incorporating nutritional state may indicate a worse long-term prognosis in CLTI patients.