Background

People with peripheral arterial disease may experience symptoms of limb ischaemia. When this occurs with walking and ceases upon rest, it is termed intermittent claudication. Symptoms of limb ischaemia can range from aches, cramps, numbness or, more commonly, pain. These symptoms can manifest anywhere in the lower limb, although the most common site is the calf muscle due to insufficient patency of the superficial femoral artery.1 ,2 In addition, these symptoms limit walking capacity (speed and distance) and in turn lower the quality of life.3 ,4 Whether symptomatic or not, peripheral arterial disease is also associated with an increased risk of cardiovascular and cerebrovascular events, death, as well as accelerated rates of bone loss and increased fracture risk.1 ,5

Several types of intervention (often in combination) are used to improve walking capacity, including medication, surgery and exercise training.1 Previous systematic reviews have established that supervised progressive exercise training can improve both maximum and pain-free walking distances, and that it is more effective in this regard than unsupervised exercise training6 and usual care or placebo.7 Although the effect of supervision is therefore clear, less is known about the influence of factors such as the duration of the training, whether the walking is done on a treadmill, and what pain threshold, if any, is used to determine when to stop walking.8 A systematic review of randomised trials comparing exercise regimens that differ by one of these factors is being undertaken.8 Until this is complete, a less direct estimate can also be obtained through meta-regression of the set of controlled trials of exercise interventions, if variation in each training factor (long vs short duration, treadmill vs floor walking, etc) is represented among the trials.9

Aims

This systematic review of randomised trials was performed to determine the effect of supervised progressive walking training on maximum walking distance and pain-free walking distance in people with intermittent claudication. The review also sought to determine the influence of training duration, use of treadmills and pain threshold.

Searches and inclusion criteria

Cochrane CENTRAL, MEDLINE and Embase were searched using terms for claudication or peripheral vascular disease and terms for exercise or walking training. To be eligible, studies were required to have used a randomised design to compare the effects of supervised walking training versus control in people with intermittent claudication and have assessed pain-free walking distance and/or maximum walking distance, or time using a treadmill test. No language restriction was applied and citation tracking of eligible studies was performed. Working independently, three reviewers applied the selection criteria and two reviewers extracted the relevant data, including information about the participants, interventions and outcomes, as well as items for rating quality and reporting on the PEDro scale.10

Main outcome measures

The review considered only maximum walking distance and pain-free walking distance. Where included studies measured walking capacity by time, for example, time walking on a treadmill at a given speed, this was converted to distance.

Statistical methods

Outcomes were meta-analysed using random-effects models and the conversion of all outcomes to distances in metres allowed the meta-analysis result to be reported in metres as mean differences with 95% CIs. Heterogeneity was assessed using the I² statistic and the likelihood of selective reporting of trials was assessed using funnel plots, Begg tests and Egger tests. The meta-regression analysed how the effect of the training is influenced by the following factors: the duration of the training programme (in weeks); the cumulative training time (in min); whether the walking was done on a treadmill; and whether patients were advised to exercise pain free, until mild to moderate pain, or to their maximum tolerable pain.

Limitations/considerations

This is a rigorous review with comprehensive list of search terms, appropriate eligibility criteria and appropriate statistical methods. The inclusion of trials that encouraged walking at home in the control group may have diluted the treatment effect slightly, although the significantly greater effect of supervised than unsupervised walking training6 and usual care or placebo7 is established.

The use of meta-regression was appropriate, given the large number of trials that were eligible for inclusion and their variation in the training factors used in the analysis. Meta-regression can be preplanned when randomised comparisons are not anticipated to be retrieved by the search strategy,11 as was the case here.

Given the importance of outcomes such as fractures, cardiovascular and cerebrovascular events, quality of life and mortality, it is disappointing that this review did not take the opportunity to assess such outcomes.

Clinical implications

Data from over 1000 participants were meta-analysed, providing reasonably precise estimates of the effect of supervised walking training in this population. Therefore clinicians can confidently recommend and administer this intervention. As large amounts of data accumulate to answer the same clinical question, it becomes less likely that additional trials would change the interpretation of the available estimate.12 Therefore researchers considering another trial of supervised walking training should first formally calculate the likelihood that this would alter the interpretation of the estimate from the meta-analysis in an updated systematic review.12

Unfortunately, the meta-regression did not identify any training factors that were independently associated with the amount of improvement in maximum walking distance or pain-free walking distance. Clinicians seeking guidance to optimise the supervised walking training they provide could instead search PEDro for trials that compare training regimens that differ in their duration, their use of treadmills and so on. Clinicians can also await the Cochrane review that is underway to identify such trials and synthesise their results.8

Clinicians should also be aware of a recent systematic review of 36 randomised trials, which found that walking training had similar efficacy on walking capacity in people with intermittent claudication as other modes of aerobic exercise such as progressive resistance training.13 Therefore other modes of aerobic exercise should be considered where patients are poorly compliant, unable to walk short distances, or where clinicians have difficulty providing supervised walking training due to limited space and resources.