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.).

Why did we conduct this research?:

Patients with intermittent claudication present with pain in the lower limbs on exercising, relieved by rest. This negatively impacts on exercise tolerance and quality of life.

Initially, such patients should be offered best medical therapy, including exercise advice, and a supervised exercise therapy programme. Supervised exercise therapy involves leg and feet exercises supervised by health-care professionals and, despite evidence favouring supervised versus unsupervised exercise, are underutilised in the United Kingdom. Therefore, there remains a significant difference between recommended standard care (best medical therapy and supervised exercise therapy) and ‘real-world’ standard care (best medical therapy only).

Neuromuscular electrical stimulation devices have emerged as safe, portable and readily accessible, with some evidence suggesting they can improve outcomes, including pain-free walking distance and quality of life. This study investigated whether a neuromuscular electrical stimulation device improved the walking distance of patients with intermittent claudication compared to local standard care available (which may include supervised exercise therapy).

What did we do?:

Two hundred patients diagnosed with intermittent claudication at 11 hospitals in England took part. A computer program randomly assigned half the patients to local standard care only, while the other half were given a neuromuscular electrical stimulation device which delivers electrical stimulation to leg and feet muscles through foot-pads, plus local standard care.

What did we find?:

There was no clear difference in maximal walking distances between those who received a device and those who didn’t. However, neuromuscular electrical stimulation improved walking distances in patients who attended a supervised exercise therapy programme (although not significant), and clearly improved walking distances in those patients with a good baseline upper walking limit. Supervised exercise therapy significantly improved walking distances.

What could be done next?:

Future research studies should further evaluate the effectiveness of neuromuscular electrical stimulation in combination with supervised exercise therapy, and in patients who have a good baseline walking distance in a larger sample of patients with intermittent claudication.

Article history

The research reported in this issue of the journal was funded by the EME programme as project number 15/180/68. The contractual start date was in November 2017. The final report began editorial review in January 2022 and was accepted for publication in August 2022. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The EME editors and production house have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.