Methods: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. Results: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. Conclusion: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC. This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.

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 < 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.).

Background This randomised controlled trial investigates the dosing effect of neuromuscular electrical stimulation (NMES) in patients with chronic venous disease (CVD). Methods Seventy-six patients with CEAP C3-C5 were randomised to Group A (no NMES), B (30 minutes of NMES daily) or C (60 minutes of NMES daily). Primary outcome was percentage change in Femoral Vein Time Averaged Mean Velocity (TAMV) at 6 weeks. Clinical severity scores, disease-specific and generic quality of life (QoL) were assessed. Results Seventy-six patients were recruited - mean age 60.8 (SD14.4) and 47:29 male. Six patients lost to follow-up. Percentage change in TAMV (p<0.001) was significantly increased in Groups B and C. Aberdeen Varicose Veins Questionnaire Score (-6.9, p=0.029) and Venous Clinical Severity Score (-4, p-0.003) improved in Group C, and worsened in Group A (+1, p=0.025). Conclusions Daily NMES usage increases flow parameters, with twice daily usage improving QoL and clinical severity at 6 weeks in CVD patients.

Objective: To assess the clinical efficacy of a neuromuscular electrical stimulation (NMES) device to improve the absolute walking distance in patients with intermittent claudication as an adjunct to the local standard care available at the study sites compared with local standard care alone. Methods: This open, multicenter, randomized controlled trial included eight participating centers in England. Sites are equally distributed between those that provide supervised exercise therapy programs and those that do not. Patients with intermittent claudication meeting the eligibility criteria and providing consent will be randomized, depending on the center type, to either NMES and locally available standard care or standard care alone. The primary end point is change in absolute walking distance at 3 months (the end of the intervention period) by treadmill testing. Secondary outcomes include quality of life, compliance with the interventions, economic evaluation of the NMES device, and lower limb hemodynamic measures to further the understanding of underlying mechanisms. Recruitment commenced in March 2018 and will continue for a total of 15 months. The Neuromuscular Electrical Stimulation Improves the Absolute Walking Distance in Patients with Intermittent Claudication trial is funded by the UK Efficacy and Mechanism Evaluation Programme, Medical Research Council, and National Institute for Health Research partnership.

Objective Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is a significant cause of morbidity and mortality, affecting one in 1000 adults per year. Neuromuscular electrical stimulation is the transcutaneous application of electrical impulses to elicit muscle contraction, preventing venous stasis. This review aims to investigate the evidence underlying the use of neuromuscular electrical stimulation in thromboprophylaxis. Methods The Medline and Embase databases were systematically searched, adhering to PRISMA guidelines, for articles relating to electrical stimulation and thromboprophylaxis. Articles were screened according to a priori inclusion and exclusion criteria. Results The search strategy identified 10 randomised controlled trials, which were used in three separate meta-analyses: five trials compared neuromuscular electrical stimulation to control, favouring neuromuscular electrical stimulation (odds ratio of deep vein thrombosis 0.29, 95% confidence interval 0.13–0.65; P = .003); three trials compared neuromuscular electrical stimulation to heparin, favouring heparin (odds ratio of deep vein thrombosis 2.00, 95% confidence interval 1.13–3.52; P = .02); three trials compared neuromuscular electrical stimulation as an adjunct to heparin versus heparin only, demonstrating no significant difference (odds ratio of deep vein thrombosis 0.33, 95% confidence interval 0.10–1.14; P = .08). Conclusion Neuromuscular electrical stimulation significantly reduces the risk of deep vein thrombosis compared to no prophylaxis. It is inferior to heparin in preventing deep vein thrombosis and there is no evidence for its use as an adjunct to heparin.

There is a significant global health and economic burden of peripheral arterial disease (PAD), which is estimated to affect 202 million people worldwide with a U.S. treatment expenditure of $4.37 billion in 2001. Symptomatic PAD most commonly presents with intermittent claudication or lower limb pain on exertion that settles with rest. This limits exercise tolerance and impairs quality of life. Management strategies include best medical therapy for cardiovascular risk-factor modification with supervised exercise, before progressing to invasive endovascular or surgical interventions. Neuromuscular electrical stimulation (NMES) is a novel emerging noninvasive technology. The Revitive IX footplate device stimulates the calf muscle pump, improving lower limb circulation. The aim of this study was to assess the efficacy of this NMES device in the management of PAD. Patients meeting the inclusion criteria were recruited from the vascular outpatient clinic. During an initial appointment, baseline measures, including the primary outcome of absolute walking distance (AWD) and secondary outcome of initial claudication distance (ICD) were determined by a treadmill test. Secondary outcomes included quality of life scores from the disease-specific Intermittent Claudication Questionnaire (ICQ) and generic EuroQoL 5D (EQ-5D) questionnaire. All patients were then instructed to undergo 30 minutes of NMES daily for 6 weeks before follow-up, and repeated measures were undertaken. Statistical significance for continuous data was calculated by paired t-test. A total of 20 consecutive patients (16 males and 4 females), with an average age of 70.8 years, completed the study protocol. The mean AWD improved significantly over the intervention period by ∼ 85 meters (102.3 vs 187.2 meters; P = .002), as did the mean ICD by 38 meters (50.5 vs 88.2 meters; P = .0008). Disease-specific ICQ scores improved from 44.3 at the baseline appointment to 35.21 (P = .009) at 6 weeks, with the EQ-5D measures also improving significantly (0.5427 vs 0.6443; P = .005) over the same period. This proof-of-concept study has shown that NMES reduces the symptom burden of PAD by improving exercise tolerance and quality of life. This data warrant a robust randomized controlled trial to assess the efficacy of NMES as a noninvasive management strategy in PAD, which may delay disease progression and therefore the need for invasive interventions. NMES devices are portable, safe, and may prove an effective strategy to reduce the global health and economic burden of PAD.