Treatment Of Intermittent Claudication Research Articles

Telephone Health Coaching and Remote Exercise Monitoring (TeGeCoach) in Peripheral Arterial Occlusive Disease.

Supervised exercise programs are used to treat intermittent claudication (IC). Home-based exercise programs have been developed to lower barriers to participation. We studied the effects of one such exercise program (TeGeCoach) on self-reported walking ability in patients with IC. In a pragmatic multicenter randomized controlled trial (registration number NCT03496948), 1982 patients with symp - tomatic IC insured by one of three German statutory health insurance funds received either telephone health coaching with remote exercise monitoring (TeGeCoach; n = 994) or routine care (n = 988). The primary outcome was the change in Walking Impairment Questionnaire (WIQ) scores after 12 and 24 months in the intention-to-treat population. The secondary outcomes were healthrelated quality of life, symptoms of depression or anxiety, health competence, patient activation, alcohol use, and nicotine depen - dence. There was a significant group difference in WIQ score in favor of TeGeCoach (p < 0.0001), amounting to 6.30 points at 12 months (Bonferroni-corrected 95% CI [4.02; 8.59], Cohen's d = 0.26) and 4.55 points at 24 months ([2.20; 6.91], d = 0.19). Some of the secondary outcomes also showed positive results in favor of TeGeCoach at 12 months with small effect sizes (d ≥ 0.20), including physical health-related quality of life and patient activation. The average daily step count was not higher in the TeGeCoach group. Significant improvements regarding symptom burden demonstrate the benefit of a home-based exercise program and thus expand the opportunities for guideline-oriented treatment of IC. Future studies should additionally address the effect of home-based exercise programs on clinical variables by means of, for example, the 6-minute walk test.

Differential scanning calorimetric evaluation of the human plasma in patients using cilostazol for the treatment of intermittent claudication (a preliminary study)

This preliminary study employs differential scanning calorimetry (DSC) to assess alterations in human plasma composition in patients treated with cilostazol for intermittent claudication. Cilostazol, an antiplatelet and vasodilator agent, is commonly prescribed to moderate symptom associated with PAD caused by reduced peripheral blood flow. Patients selected according to study protocol were treated with cilostazol for a duration of three months. At the visits, subjects exercised by a standard walking test controlled by physiotherapist. The blood samples were taken on day 0 (control), day 15, 1, 2 and 3 months. Through DSC analysis, we investigate potential thermodynamic changes in plasma composition induced by cilostazol treatment. As a result of the treatment, the pain-free walking distance improved significantly in the first 3 months. The thermal unfolding of the human plasma showed a correlation with the walking improvement. Our findings provide insights into the systemic effects of cilostazol and its impact on plasma constituents in the context of PAD and intermittent claudication management.

Long-term patient-reported outcomes among patients undergoing revascularization vs medical therapy for intermittent claudication

ObjectiveSociety for Vascular Surgery guidelines recommend revascularization for patients with intermittent claudication (IC) if it can improve patient function and quality of life. However, it is still unclear if patients with IC achieve a significant functional benefit from surgery compared with medical management alone. This study examines the relationship between IC treatment modality (operative vs nonoperative optimal medical management) and patient-reported outcomes for physical function (PROMIS-PF) and satisfaction in social roles and activities (PROMIS-SA). MethodsWe identified patients with IC who presented for index evaluation in a vascular surgery clinic at an academic medical center between 2016 and 2021. Patients were stratified based on whether they underwent a revascularization procedure during follow-up vs continued nonoperative management with medication and recommended exercise therapy. We used linear mixed-effect models to assess the relationship between treatment modality and PROMIS-PF, PROMIS-SA, and ankle-brachial index (ABI) over time, clustering among repeat patient observations. Models were adjusted for age, sex, diabetes, Charlson Comorbidity Index, Clinical Frailty Score, tobacco use, and index ABI. ResultsA total of 225 patients with IC were identified, of which 40% (n = 89) underwent revascularization procedures (42% bypass; 58% peripheral vascular intervention) and 60% (n = 136) continued nonoperative management. Patients were followed up to 6.9 years, with an average follow-up of 5.2 ± 1.6 years. Patients who underwent revascularization were more likely to be clinically frail (P = .03), have a lower index ABI (0.55 ± 0.24 vs 0.72 ± 0.28; P < .001), and lower baseline PROMIS-PF score (36.72 ± 8.2 vs 40.40 ± 6.73; P = .01). There were no differences in patient demographics or medications between treatment groups. Examining patient-reported outcome trends over time; there were no significant differences in PROMIS-PF between groups, trends over time, or group differences over time after adjusting for covariates (P = .07, P = .13, and P =.08, respectively). However, all patients with IC significantly increased their PROMIS-SA over time (adjusted P = .019), with patients managed nonoperatively more likely to have an improvement in PROMIS-SA over time than those who underwent revascularization (adjusted P = .045). ConclusionsPatient-reported outcomes associated with functional status and satisfaction in activities are similar for patients with IC for up to 7 years, irrespective of whether they undergo treatment with revascularization or continue nonoperative management. These findings support conservative long-term management for patients with IC.

Cilostazol for peripheral arterial disease - a position paper from the Italian Society for Angiology and Vascular Medicine.

Cilostazol is a quinolinone-derivative selective phosphodiesterase inhibitor and is a platelet-aggregation inhibitor and arterial vasodilator for the symptomatic treatment of intermittent claudication (IC). Cilostazol has been shown to improve walking distance for patients with moderate to severe disabling intermittent claudication who do not respond to exercise therapy and who are not candidates for vascular surgical or endovascular procedures. Several studies evaluated the pharmacological effects of cilostazol for restenosis prevention and indicated a possible effect on re-endothelialization mediated by hepatocyte growth factor and endothelial precursor cells, as well as inhibiting smooth muscle cell proliferation and leukocyte adhesion to endothelium, thereby exerting an anti-inflammatory effect. These effects may suggest a potential effectiveness of cilostazol in preventing restenosis and promoting the long-term outcome of revascularization interventions. This review aimed to point out the role of cilostazol in treating patients with peripheral arterial disease, particularly with IC, and to explore its possible role in restenosis after lower limb revascularization.

The Use and Impact of Cilostazol on Patients Undergoing Endovascular Peripheral Interventions

ObjectivesCilostazol is used for the treatment of intermittent claudication. The impact of cilostazol on the outcomes of peripheral vascular interventions (PVI) remains controversial. This study assesses the use and impact of cilostazol on patients undergoing PVI for peripheral arterial disease (PAD). MethodsThe Vascular Quality Initiative (VQI) database files for PVI were reviewed. Patients with PAD who underwent PVI for CLTI or claudication were included and divided based on the use of cilostazol preoperatively. After propensity matching for patient demographics and comorbidities, the short-term and long-term outcomes of the two groups (preoperative cilostazol use versus no pre-operative cilostazol use) were compared. The Kaplan-Meier method was used to determine outcomes. ResultsA total of 245,309 patients underwent PVI procedures and 6.6% (N=16,366) were on cilostazol prior to intervention. Patients that received cilostazol were more likely to be male (62% vs 60%; P < .001), White (77% vs 75%; P < .001), and smokers (83% vs 77%; P < .001). They were less likely to have diabetes mellitus (50% vs 56%; P < .001) and congestive heart failure (14% vs 23%; P < .001). Patient on cilostazol were more likely to be treated for claudication (63% vs 40%, P < .001), undergo prior lower extremity revascularization (55% vs 51%, P<.001) and less likely to have undergone prior minor and major amputation (10% vs 19%; P < .001) compared to patients who did not receive cilostazol. After 3:1 propensity matching, there were 50,265 patients included in the analysis with no differences in baseline characteristics. Patients on cilostazol were less likely to develop renal complications and more likely to be discharged home. Patients on cilostazol had significantly lower rates of long-term mortality (11.5% vs 13.4%, P <.001 and major amputation (4.0% vs 4.7%, P=0.022). However, there were no significant differences in rates of reintervention, major adverse limb events, or patency after PVI. Amputation-free survival rates were significantly higher for patients on cilostazol, after four years of follow-up (89% vs 87%, P=0.03). ConclusionCilostazol is underutilized in the VQI database and seems to be associated with improved amputation-free survival. Cilostazol therapy should be considered in all patients with PAD who can tolerate it prior to PVI.

The anti-platelet drug cilostazol enhances heart rate and interrenal steroidogenesis and exerts a scant effect on innate immune responses in zebrafish.

Cilostazol, an anti-platelet phosphodiesterase-3 inhibitor used for the treatment of intermittent claudication, is known for its pleiotropic effects on platelets, endothelial cells and smooth muscle cells. However, how cilostazol impacts the endocrine system and the injury-induced inflammatory processes remains unclear. We used the zebrafish, a simple transparent model that demonstrates rapid development and a strong regenerative ability, to test whether cilostazol influences heart rate, steroidogenesis, and the temporal and dosage effects of cilostazol on innate immune cells during tissue damage and repair. While dosages of cilostazol from 10 to 100 μM did not induce any noticeable morphological abnormality in the embryonic and larval zebrafish, the heart rate was increased as measured by ImageJ TSA method. Moreover, adrenal/interrenal steroidogenesis in larval zebrafish, analyzed by whole-mount 3β-Hsd enzymatic activity and cortisol ELISA assays, was significantly enhanced. During embryonic fin amputation and regeneration, cilostazol treatments led to a subtle yet significant effect on reducing the aggregation of Mpx-expressing neutrophil at the lesion site, but did not affect the immediate injury-induced recruitment and retention of Mpeg1-expressing macrophages. Our results indicate that cilostazol has a significant effect on the heart rate and the growth as well as endocrine function of steroidogenic tissue; with a limited effect on the migration of innate immune cells during tissue damage and repair.

Angioplasty with Sirolimus-coated Balloon: the New Standard in the Treatment of PAD?

Endovascular revascularisation with paclitaxel-coated balloons for the treatment of peripheral artery disease has been shown to be an effective therapeutic option in the femoropopliteal segment. The antiproliferative effect of paclitaxel prevents restenosis. In contrast, in the infra-popliteal segment, the evidence is currently conflicting. However, there is evidence of an increased risk of amputation and mortality from the second year after angioplasty with paclitaxel-coated balloons. This may be due to a dose-dependent cytotoxic effect of paclitaxel. Sirolimus-coated balloons might therefore be an alternative because sirolimus is cytostatic rather than cytotoxic and thus has a wide therapeutic window.Three single-arm pilot studies (50, 25, and 50 patients, respectively) show that angioplasty with sirolimus-coated balloons leads to comparable results to those reported from paclitaxel-coated balloons (late lumen loss at 6 months: 0.29mm; primary patency at 12 months: femoropopliteal 79%-82%, infra-popliteal 59%; freedom from target lesion revascularization at 12 months: femoropopliteal 83%-94%, infra-popliteal 86%). Randomised controlled trials comparing standard balloon angioplasty and paclitaxel-coated balloons for the treatment of intermittent claudication or chronic limb-threatening ischaemia are active and are expected to provide efficacy and safety results from mid 2024.This review presents the results of pilot studies on angioplasty with sirolimus-coated balloons for the treatment of peripheral artery disease and reviews currently ongoing randomised controlled trials.

Application of deep oscillation therapy in the treatment of peripheral arterial diseases

Intermittent claudication is a common symptom of peripheral arterial disease, affecting up to 50% of patients over the age of 50, which is characterized by pain, discomfort, and cramping in the leg muscles during physical activity. Intermittent claudication is a common symptom of lower extremity arterial disease (LEAD), which significantly impacts patients’ quality of life and drives healthcare costs. Current treatments for intermittent claudication are often inadequate, leading to a need for more effective treatments. Developing new treatments is critical to improve outcomes for patients and address the public health implications of LEAD. This study’s aim was to present the impact of comprehensive physiotherapy, conducted independently, with the supervision of a physiotherapist, for 14 weeks, on a patient with intermittent claudication caused by peripheral arterial disease. The therapy included bicycle training in a form of physical therapy at home, combined with deep oscillation therapy. Deep oscillation therapy involved the use of an electrostatic field with a frequency of 5 to 250 Hz. The field was applied following the lymphatic drainage methodology. In the discussed case, a statistically significant and favourable increase in the measured variables was observed, such as the increase of bone-brachial index from 0.65 to 0.8, the increase of tissue perfusion, measured by laser Doppler flowmetry, from 12.3% to 61%, depending on the measurement site, and the increase in pain-free walking distance by 451%. TcPO2 measurement in the affected leg increased from 31 to 48 mmHg. The use of physical therapy at home combined with deep oscillation showed improvements in pain-free walking distance, Ankle Brachial Index, and other measures in patients with peripheral arterial disease. Deep oscillation therapy demonstrated potential analgesic effects but also raised concerns about possible nerve damage. The study indicated that physical therapy at home might serve as an alternative to supervised exercise therapy, but it had limitations like a small sample size and lack of direct comparisons.

Subacute administration of cilostazol modulates PLC-γ/PKC-α/p38/NF-kB pathway and plays vascular protective effects through eNOS activation in early stages of atherosclerosis development

AimsHypercholesterolemia is an important risk factor for development of cardiovascular disturbances, such as atherosclerosis, and its treatment remains challenging in modern medicine. Cilostazol is a selective inhibitor of phosphodiesterase 3 clinically prescribed for intermittent claudication treatment. Due to its pleiotropic properties, such as lipid lowering, anti-inflammatory, and antioxidant effects, the therapeutic repurposing of cilostazol has become a strategic approach for atherosclerosis treatment. This study aimed to investigate the effects of subacute administration of cilostazol on the aortas of hypercholesterolemic rats, focusing on the signaling pathways involved in these actions. Main methodsA murine model of hypercholesterolemia was employed to mimic the early stages of atherosclerosis development. Vascular reactivity assays were performed on thoracic aorta rings to assess the vascular response, as well as the non-invasive blood pressure was evaluated by plethysmography method. Pro-inflammatory markers and malondialdehyde (MDA) levels were measured to investigate the anti-inflammatory and antioxidant effects of cilostazol. Western Blot analysis was performed in aortas homogenates to evaluate the role of cilostazol on PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB and PKA/eNOS/PKG pathways. Key findingsThe hypercholesterolemic diet induced the production of pro-inflammatory mediators such as TNF-α, TXB2, VCAM, and worsened vascular function, marked by increased contractile response, decreased maximum relaxation, and elevated systolic and diastolic blood pressure. Cilostazol seems to counteract the deleterious effects promoted by hypercholesterolemic diet, showing important anti-inflammatory and vasculoprotective properties possibly through the inhibition of the PLC-γ/PKC-α/p38-MAPK/IκB-α/NF-кB pathway and activation of the PKA/eNOS/PKG pathway. SignificanceCilostazol suppressed hypercholesterolemia-induced vascular dysfunction and inflammation. Our data suggest the potential repurposing of cilostazol as a pharmacological treatment for atherosclerosis.

Cost-Effectiveness of Exercise Therapy in Patients with Intermittent Claudication-A Comparison of Supervised Exercise, Home-Based Structured Exercise, and Walk Advice from the SUNFIT Trial.

Hospital-based supervised exercise (SEP) is a guideline-recommended intervention for patients with intermittent claudication (IC). However, due to the limited availability of SEP, home-based structured exercise programs (HSEP) have become increasingly popular alongside the "go home and walk" advice. We evaluated the cost-effectiveness of walk advice (WA) with Nordic pole walking vs. SEP combined with WA or HSEP combined with WA. We used data from the SUNFIT RCT (NCT02341716) to measure quality-adjusted life-years (QALYs) over a 12-month follow-up, and economic costs were obtained from a hospital cost-per-patient accounting system. Incremental cost-effectiveness ratios (ICERs) were calculated, and uncertainty was assessed using nonparametric bootstrapping. The average health-care-cost per patient was similar in the WA (EUR 1781, n = 51) and HSEP (EUR 1820, n = 48) groups but higher in the SEP group (EUR 4619, n = 50, p-value < 0.01). Mean QALYs per patient during the follow-up were similar with no statistically significant differences. The findings do not support SEP as a cost-effective treatment for IC, as it incurred significantly higher costs without providing additional health improvements over WA with or without HSEP during the one-year observation period. The analysis also suggested that HSEP may be cost-effective compared to WA, but only with a 64% probability.

Neuromuscular electrical stimulation as an adjunct to standard care in improving walking distances in intermittent claudication patients: the NESIC RCT

Background Peripheral arterial disease is common and associated with increased cardiovascular morbidity and mortality. While patients with peripheral arterial disease are known to benefit from supervised exercise therapy, it is not always available. Neuromuscular electrical stimulation devices may offer a similar benefit. A randomised controlled trial was required to ascertain whether such devices can benefit patients who receive supervised exercise therapy and those who do not. Objective(s) The primary objective was to assess the mean difference in absolute walking distance at 3 months in intermittent claudication patients receiving either a neuromuscular electrical stimulation device and local standard care (intervention), or local standard care alone (control). Design A pragmatic, multicentre, randomised controlled trial stratified by centre. Setting Secondary-care National Health Service hospitals in the United Kingdom. Participants Patients aged ≥18 years, with a diagnosis of intermittent claudication according to the Edinburgh Claudication Questionnaire and ankle–brachial pressure index (or stress test), without contraindications to neuromuscular electrical stimulation were deemed eligible to partake. Interventions Participants were randomised 1 : 1 to either local standard care or local standard care and neuromuscular electrical stimulation. Due to the nature of the intervention, it was unfeasible to blind the research nurse or participant to the study allocation. Main outcome measures The primary outcome measure was absolute walking distance measured by treadmill testing at 3 months. Secondary outcomes included change in initial claudication distance, quality of life, compliance with interventions and haemodynamic assessments. Results Two hundred patients underwent randomisation, with 160 patients having analysable primary outcome data for the intention-to-treat analysis intervention (n = 80); control (n = 80). As the data were right-censored, a Tobit regression model was used to analyse the primary outcome, utilising the square root of the absolute walking distance to accommodate the skewed data. However, as this made the data difficult to interpret, a Tobit regression model using raw absolute walking distance data was used as well. Neuromuscular electrical stimulation improved the difference in absolute walking distance at 3 months but this was not statistically significant (square root of absolute walking distance: 0.835 units, 95% confidence interval −0.67 to 2.34 units; p = 0.28/absolute walking distance raw data: 27.18 m, 95% confidence interval −26.92 to 81.28 m; p = 0.323). Supervised exercise therapy participants showed a markedly improved absolute walking distance compared with patients receiving best medical therapy only at 3 months (square root of absolute walking distance: 3.295 units 95% confidence interval 1.77 to 4.82; p &lt; 0.001/absolute walking distance raw data: 121.71 m, 95% confidence interval 67.32 to 176.10; p ≤ 0.001). Neuromuscular electrical stimulation significantly improved absolute walking distance at 3 months for mild claudicants (square root of absolute walking distance: 2.877 units, 95% confidence interval 0.51 to 5.25; p = 0.019/absolute walking distance raw data: 120.55 m, 95% confidence interval 16.03 to 225.06; p = 0.03) compared to the control arm. This was an unplanned (post hoc) analysis. There were no clear differences in mechanistic measurements between the two treatment groups over the follow-up period. Serious adverse events were evenly reported between the two groups; all being classified as either not related or unlikely to be related to the study device. Limitations Absolute walking distance was used as the primary outcome measure; there was a large range of baseline distances in both groups with right-skewed distribution. We did not stratify by baseline absolute walking distance for the primary outcome analysis. Additionally, only 160 patients had analysable primary outcome data due to missing treadmill data. Conclusions Supervised exercise therapy is an effective treatment for intermittent claudication. Neuromuscular electrical stimulation appears to be beneficial as an adjunct to supervised exercise therapy and on its own in mild claudicants. Future work Further studies are needed to confirm the effectiveness of neuromuscular electrical stimulation in combination with supervised exercise therapy, and in mild to moderate claudicants in a larger sample size. Study registration This trial is registered as ISRCTN18242823. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership (project number 15/180/68). This will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 2. See the NIHR Journals Library website for further project information. Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC) (with others, e.g. NIHR Imperial CRF, Imperial College ECMC, NIHR Imperial PSTRC, NIHR London MIC, etc.).

The Use and Impact of Cilostazol on Patients Undergoing Peripheral Vascular Interventions

Cilostazol is used for the treatment of intermittent claudication. The impact of cilostazol on the outcomes of peripheral vascular interventions (PVIs) remains controversial. This study assesses the use and impact of cilostazol on patients undergoing PVI for peripheral arterial disease (PAD). The Vascular Quality Initiative (VQI) database files for PVI were reviewed. Patients who underwent PVI for PAD were included and divided based on the use of cilostazol preoperatively. After propensity matching for patient demographics and comorbidities, the short-term and long-term outcomes of the two groups were compared. A total of 183,661 patients underwent PVI procedures, and 6.5% (n = 12,014) of them were on cilostazol preoperatively. PVI was performed for claudication in 62% (n = 6174) on cilostazol. Patients that received cilostazol were more likely to be White (77% vs 75%; P < .001) and smokers (84% vs 77%; P < .001). They were more likely to undergo balloon angioplasty (39% vs 31%; P < .001) and less likely to have diabetes mellitus (50% vs 56%; P < .001), congestive heart failure (14% vs 22%; P < .001), and prior amputation (10% vs 19%; P < .001) compared with patients who did not receive cilostazol. After 3:1 propensity matching, there were 37,304 patients included in the analysis. Patients receiving cilostazol had significantly higher incidence of dissection (3.3% vs 2.6%; P = .007) with but were more likely to be discharged home (95% vs 94%; P < .001). Patients on cilostazol had lower rates of long-term mortality (10% vs 12%; P = .003). There were no significant differences in rates of major amputation, reintervention, major adverse limb events, or patency rates after PVI (Table). Amputation-free survival rates were significantly higher for patients on cilostazol, after 4 years of follow-up (90% vs 88%; P = .03) (Fig). Cilostazol is underutilized in the VQI database and seems to be associated with improved amputation-free survival. Cilostazol therapy should be considered in all patients with PAD who can tolerate it prior to PVI.TableCharacteristics and outcomes of patients treated with PVI with and without cilostazol after propensity matchingCharacteristicsNo cilostazol, n = 27,978Cilostazol, n = 9326P-valueaSMDDemographics Age, years68 ± 1068 ± 100.015 Female sex10,108 (36)3446 (37)0.017 Race0.059White21,857 (78)7054 (76)African American4231 (15)1581 (17)Other1890 (6.8)691 (7.4) Hispanic1611 (5.8)675 (7.2) Body mass index, kg/m228.2 ± 6.128.1 ± 6 Living status0.016Nursing home/homeless492 (1.8)184 (2.0) Function0.043Independent21,987 (79)7165 (77)Assisted5248 (19)1885 (20)Non-ambulatory743 (2.7)276 (3.0)Comorbidities Hypertension25,127 (90)8433 (90)0.03 Diabetes14,279 (51)4856 (52)0.021 Smoking23,136 (83)7623 (82)0.025 Chronic obstructive pulmonary disease7489 (27)2595 (28)0.024 Congestive heart failure3764 (13)1321 (14)0.021 Cardiovascular disease4000 (14)1132 (12) Coronary artery disease9792 (35)3396 (36)0.03 Coronary artery bypass graft5464 (20)1979 (21)<.001 Percutaneous coronary intervention7195 (26)2475 (27).11 Renal status0.034Chronic kidney disease21,203 (76)6937 (74)End-stage renal disease1210 (4.3)411 (4.4) Prior lower-extremity revascularization15,927 (57)5408 (58)0.021 Prior amputation2926 (10)1054 (11).022 Prior coronary artery stenting/carotid endarterectomy2465 (8.8)852 (9.1).3 Prior aneurysm894 (3.2)190 (2.0)<.001Medications Angiotensin-converting enzyme inhibitor15,563 (56)5481 (59)<.001 Aspirin20,786 (74)7387 (79)<.001 Statin21,593 (77)7837 (84)<.001 P2Y12 inhibitors13,409 (48)4964 (53)<.001 Anticoagulation5163 (18)1441 (15)<.001Procedural characteristics Indication0.008Claudication17,384 (62)5833 (63)Chronic limb-threatening ischemia10,594 (38)3493 (37) Urgency0.055Elective25,485 (91)8344 (89)Urgent/emergent2493 (8.9)982 (11) Fluoroscopy time, minutes14 (8-22)15 (9-24)<.001OutcomesNo cilostazol, n = 16,619bCilostazol, n = 5435b Periprocedural outcomesTechnical success15,461 (95)5105 (95).9Thrombosis99 (0.6)28 (0.5).5Dissection428 (2.6)177 (3.3).007Hematoma349 (2.1)121 (2.2).6 Surgical length of stay, days2.2 ± 15.41.6 ± 7.1.052 Systemic complicationsCardiac169 (1.0)48 (0.9).4Myocardial infarction54 (0.3)13 (0.2).3Pulmonary48 (0.3)16 (0.3)>.9Renal85 (0.5)23 (0.4).4Infection13 (<0.1)3 (<0.1).8 30-day mortality122 (0.7)28 (0.5).088 Discharge status<.001Home15,537 (94)5165 (95)Rehab unit447 (2.7)104 (1.9)Others609 (3.7)157 (2.9)Long-term outcomes Follow-up time, days393 ± 183396 ± 174.2 Reintervention1971 (16)641 (15).3 Secondary patency8675 (90)3042 (91).4 Major amputation571 (4.5)166 (3.8).059 Major adverse limb events2415 (19)780 (18).13 Mortality1928 (12)550 (10).003SMD, Standardized mean differences for variables used in propensity-matching.Data are expressed as median (interquartile range), number (%), or mean ± standard deviation.Boldface P values indicates statistically significant difference for P < .05 and SMD >0.1.aWilcoxon rank sum test; Pearson χ- test.bSample numbers changed due to loss to follow-up. 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A Double Blind, Placebo Controlled, Randomised Trial of Extracorporeal Shockwave Therapy as a Novel Treatment For Intermittent Claudication

Objective: Peripheral occlusive arterial disease affects 202 million people worldwide, with intermittent claudication as its most prevalent manifestation. The recommended management for non-life limiting intermittent claudication is conservative and includes best medical therapy in the form of antiplatelet and statin therapy, smoking cessation, and supervised exercise. However, provision of supervised exercise programmes and uptake among intermittent claudication patients is very poor. Extracorporeal shockwave therapy (ESWT) technology has been adapted from renal lithotripsy to a variety of musculoskeletal uses and in vitro and in vivo data has shown improved perfusion of the myocardium and hind leg in the setting of arterial ischaemia. Pilot data has demonstrated that ESWT is effective for improving walking distances in patients with intermittent claudication.1 This study aims to consider its effectiveness for improving quality of life in patients with intermittent claudication.

How German vascular surgeons and angiologists judge walking exercise for patients with PAD.

Background: To determine the physician's perspective and perception on walking exercise as well as barriers in guideline-directed best medical treatment of patients with lower extremity peripheral arterial disease (PAD). Patients and methods: All members of the German Society for Vascular Surgery and Vascular Medicine and of the German Society for Angiology - Society for Vascular Medicine with valid email address were invited to participate in an electronic survey on walking exercise for treatment of intermittent claudication that was developed by the authors. Results: Amongst 3910 invited participants, 743 (19%) provided valid responses (33% females, 84% vascular surgery, 15% angiology). Thereof, 65% were employed by non-university hospitals, 16% by university institutions, and 18% by outpatient facilities. A mean of 14 minutes were spent per patient to counsel and educate, while only 53% responded they had enough time in everyday clinical practice. While 98% were aware of the beneficial impact of structured exercise training (SET) on pain free walking distance and 90% advise their patients to adhere to SET, only 44% provided useful guidance to patients to find local SET programmes and merely 42% knew how to prescribe SET as service that can be reimbursed by medical insurances. Approximately 35% knew a local SET programme and appropriate contact person. Health-related quality of life was assessed in a structured way by only 11%. Forty-seven percent responded that medical insurances should be responsible to implement and maintain SET programmes, while only 4% held hospital physicians responsible to achieve this task. Conclusions: This nationwide survey study amongst vascular specialists illustrates the current insufficient utilisation of SET as an evidence-based therapeutic cornerstone in patients with lower extremity PAD in Germany. The study also identified several barriers and flaws from the physician's perspectives which should be addressed collectively by all health care providers aiming to increase the SET use and eventually its' impact on patients with PAD.

Lack of patient-centered evaluation of outcomes in intermittent claudication literature

BackgroundPeripheral arterial disease, characterized as arterial atherosclerotic disease, can lead to insufficient flow in the lower extremities and ischemia, with the most common clinical manifestation being intermittent claudication (IC). In 2022, the Society for Vascular Surgery (SVS) developed appropriate use criteria for the management of IC that used this systematic review as a source of evidence. The objective of this study is to synthesize the findings of the systematic review and identify evidence gaps. MethodsA comprehensive search of literature databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted from January 1, 2000, to November 30, 2022. Noncomparative and comparative observational studies and randomized controlled trials were included. Included studies evaluated exercise therapy, endovascular or open revascularization for the treatment of IC. Outcomes of interest (freedom from major adverse limb event, health-related quality of life, and walking distance) were compared in various subgroups (age, sex, diabetes, smoking status, anatomical location of disease, and optimal medical therapy). ResultsTwenty-six studies reported the outcomes of interest for the evidence map. The general conclusions of the studies that reported freedom from major adverse limb events were that reintervention rates for endovascular therapy at ≥2 years were >20%, major amputation rates were often not reported, and, after endovascular therapy, the 1-month mortality was low (<2%). Quality of life and walking distance data were sparse, limited to only endovascular intervention, and insufficient to make any strong conclusions. ConclusionsIC in patients with peripheral arterial disease poses a significant socioeconomic and health care burden. Major, consequential gaps exist in the IC literature with respect to the assessment of patient reported outcome measures, standardized measures of walking distance and the comparative effectiveness of initial exercise therapy vs invasive intervention. The evidence gaps identified by the Society for Vascular Surgery appropriate use criteria on IC systematic review serve as a guide for future research efforts to optimize care for this patient population.

A Novel Way to Enhance Compliance in the Conservative Treatment of Intermittent Claudication (IC) Patients with the Help of Remote Monitoring

A Novel Way to Enhance Compliance in the Conservative Treatment of Intermittent Claudication (IC) Patients with the Help of Remote Monitoring

Supervised exercise therapy apps for claudication

Peripheral arterial disease (PAD) has been recognised as a healthcare burden affecting up to 5.56% of the global population over 25 years of age.1 Intermittent claudication (IC) is often debilitating and results in reduced physical activity which is associated with increased cardiovascular disease and all-cause mortality.2,3 Early identification and management of PAD is essential to improve symptoms and prevent a downward trajectory towards limb loss. Supervised exercise therapy (SET) is the widely recommended first- line treatment for IC. Despite the benefits of SET, uptake and adherence rates are recognised to be poor.4 The reasons for poor SET compliance are multifactorial and include time constraints, travelling distance, personal, financial and institutional barriers.5 To overcome these barriers, alternative methods for delivering SET need to be explored.

Carbohydrate-Derived Polytriazole Nanoparticles Enhance the Anti-Inflammatory Activity of Cilostazol.

Poly(amide-triazole) and poly(ester-triazole) synthesized from d-galactose as a renewable resource were applied for the synthesis of nanoparticles (NPs) by the emulsification/solvent evaporation method. The NPs were characterized as stable, spherical particles, and none of their components, including the stabilizer poly(vinyl alcohol), were cytotoxic for normal rat kidney cells. These NPs proved to be useful for the efficient encapsulation of cilostazol (CLZ), an antiplatelet and vasodilator drug currently used for the treatment of intermittent claudication, which is associated with undesired side-effects. In this context, the nanoencapsulation of CLZ was expected to improve its therapeutic administration. The carbohydrate-derived polymeric NPs were designed taking into account that the triazole rings of the polymer backbone could have attractive interactions with the tetrazole ring of CLZ. The activity of the nanoencapsulated CLZ was measured using a matrix metalloproteinase model in a lipopolysaccharide-induced inflammation system. Interestingly, the encapsulated drug exhibited enhanced anti-inflammatory activity in comparison with the free drug. The results are very promising since the stable, noncytotoxic NP systems efficiently reduced the inflammation response at low CLZ doses. In summary, the NPs were obtained through an innovative methodology that combines a carbohydrate-derived synthetic polymer, designed to interact with the drug, ease of preparation, adequate biological performance, and environmentally friendly production.

Systematic review the efficacy and safety of cilostazol, pentoxifylline, beraprost in the treatment of intermittent claudication: A network meta-analysis.

To evaluate the efficacy and safety of cilostazol, pentoxifylline, beraprost for intermittent claudication due to lower extremity arterial occlusive disease. Randomized controlled clinical trials were identified from PubMed, Scopus, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wanfang and Chongqing VIP databases, from the database inception to 31/12/2021. The outcome measures were walking distance measured by treadmill (maximum and pain-free walking distance), ankle-brachial index and adverse events. The quality of included studies was assessed by the Cochrane bias risk assessment tool. A network meta-analysis was carried out with Stata 16.0 software. There were 29 RCTs included in the study, covering total 5352 patients. Cilostazol was ranked first for both maximum and pain-free walking distance, followed by beraprost and pentoxifylline. For cilostazol, pentoxifylline and beraprost, maximum walking distance increased by 62.93 95%CI(44.06, 81.79), 32.72 95%CI(13.51, 55.79) and 43.90 95%CI(2.10, 85.71) meters, respectively relative to placebo, and pain-free walking distance increased by 23.92 95%CI(11.24, 36.61), 15.16 95%CI(2.33, 27.99) and 19.78 95%CI(-3.07, 42.62) meters. For cilostazol, pentoxifylline, beraprost and cilostazol combined with beraprost, ankle-brachial index increased by 0.06 95%CI(0.04, 0.07), -0.01 95%CI(-0.08, 0.05), 0.18 95%CI(0.12, 0.23) and 0.23 95%CI(0.18, 0.27), respectively relative to placebo. The pentoxifylline and cilostazol was associated with a lower ratio of adverse events than beraprost and cilostazol combined with beraprost. Cilostazol, pentoxifylline and beraprost were all effective treatments for intermittent claudication; cilostazol with good tolerance was likely to be the most effective in walking distance, while beraprost and cilostazol combined with beraprost were more prominent in the ankle-brachial index.

Credibility, Accuracy, and Comprehensiveness of Readily Available Internet-Based Information on Treatment and Management of Peripheral Artery Disease and Intermittent Claudication: Review.

Peripheral artery disease (PAD) affects millions of people worldwide, and a core component of management of the condition is self-management. The internet is an important source of health information for many people. However, the content of websites regarding treatment recommendations for PAD has not been fully evaluated. This study aimed to assess the credibility, accuracy, and comprehensiveness of websites found via a common search engine, by comparing the content to current guidelines for treatment and management of PAD and intermittent claudication (IC). A review of websites from hospitals, universities, governments, consumer organizations, and professional associations in the United States and the United Kingdom was conducted. Website recommendations for the treatment of PAD and IC were coded in accordance with the guidelines of the National Institute for Health and Care Excellence (NICE) and the American Heart Association (AHA). Primary outcomes were website credibility (4-item Journal of the American Medical Association benchmark), website accuracy (in terms of the percentage of accurate recommendations), and comprehensiveness of website recommendations (in terms of the percentage of guideline recommendations that were appropriately covered). Secondary outcomes were readability (Flesch-Kincaid grade level) and website quality (Health On the Net Foundation's code of conduct). After screening, 62 websites were included in this analysis. Only 45% (28/62) of websites met the credibility requirement by stating they were updated after the NICE guidelines were published. Declaration of authorship and funding and the presence of reference lists were less commonly reported. Regarding accuracy, 81% (556/685) of website recommendations were deemed accurate on following NICE's and the AHA's recommendations. Comprehensiveness was low, with an average of 40% (25/62) of guideline treatment recommendations being appropriately covered by websites. In most cases, readability scores revealed that the websites were too complex for web-based consumer health information. Web-based information from reputable sources about the treatment and management of PAD and IC are generally accurate but have low comprehensiveness, credibility, and readability.