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Review
Exercise training for intermittent claudication: a narrative review and summary of guidelines for practitioners
  1. Amy E Harwood1,2,
  2. Sean Pymer3,
  3. Lee Ingle4,
  4. Patrick Doherty5,
  5. Ian C Chetter3,
  6. Belinda Parmenter6,
  7. Christopher D Askew7,8,
  8. Gary A Tew9
  1. 1 Centre for Sport and Exercise Life Sciences, Coventry University, Coventry, UK
  2. 2 Faculty of Health Sciences, University of Hull, Hull, UK
  3. 3 Academic Vascular Unit, Hull York Medical School, Hull, UK
  4. 4 Department of Sport, Health and Exercise Science, University of Hull, Hull, UK
  5. 5 Department of Health Sciences, University of York, York, UK
  6. 6 Department of Exercise Physiology, Faculty of Medicine, University of New South Wales, Sydney, Australia
  7. 7 School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore DC, Australia
  8. 8 Sunshine Coast Hospital and Health Service, Birtinya, Australia
  9. 9 Department of Sport, Exercise and Rehabilitation, Northumbria University, Newcastle upon Tyne, UK
  1. Correspondence to Amy Harwood; amy.harwood{at}coventry.ac.uk

Abstract

Peripheral artery disease (PAD) is caused by atherosclerotic narrowing of the arteries supplying the lower limbs often resulting in intermittent claudication, evident as pain or cramping while walking. Supervised exercise training elicits clinically meaningful benefits in walking ability and quality of life. Walking is the modality of exercise with the strongest evidence and is recommended in several national and international guidelines. Alternate forms of exercise such as upper- or lower-body cycling may be used, if required by certain patients, although there is less evidence for these types of programmes. The evidence for progressive resistance training is growing and patients can also engage in strength-based training alongside a walking programme. For those unable to attend a supervised class (strongest evidence), home-based or ‘self-facilitated’ exercise programmes are known to improve walking distance when compared to simple advice. All exercise programmes, independent of the mode of delivery, should be progressive and individually prescribed where possible, considering disease severity, comorbidities and initial exercise capacity. All patients should aim to accumulate at least 30 min of aerobic activity, at least three times a week, for at least 3 months, ideally in the form of walking exercise to near-maximal claudication pain.

  • Exercise physiology
  • Cardiovascular
  • Review
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjsem-2020-000897

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    INTRODUCTION

    Lower-limb peripheral artery disease (PAD) is an atherosclerotic cardiovascular disease in which the arteries that carry blood to the legs and feet become hardened, narrowed and/or obstructed by the build-up of atheroma.1 PAD is a common problem thought to affect over 200 million people worldwide.2 The total disease prevalence is approximately 13% of adults >50 years old, with major risk factors including smoking, diabetes and dyslipidaemia.3

    The most classic symptom of PAD is intermittent claudication (IC). This is ischaemic muscle pain that usually presents in the calves (but can include the thighs or buttocks), is precipitated by exertion and relieved with rest (figure 1).4 This pain is thought to be due to a mismatch between the oxygen demand (of the working muscle) and an inadequate blood supply (due to the narrowed arterial pathway).5

    Figure 1
    Figure 1

    Intermittent claudication due to peripheral artery disease. Reproduced from Morlet et al3 with permission from BMJ Publishing Group Ltd. Note: Iliac or femoral artery disease can cause symptoms at multiple distal muscle sites.

    Although PAD is progressive (in the pathological sense), the clinical course is relatively stable.6 However, patients with PAD have a higher burden of cardiovascular disease and are at greater risk of major cardiovascular events.7 Another major issue for many patients is the severe decline in functional capacity (V̇O2Peak) which are comparable to patients with heart failure and reduced ejection fraction.8 The reduction in functional capacity is commonly caused by a decline in walking capacity, which may be up to less than 50% of healthy aged-matched controls.9 Factors influencing the walking distance or speed at which symptoms occur are multifactorial and include the site and severity of disease, walking pace, terrain, incline and footwear.10 These physical constraints in turn have negative connotations on patient’s mental health and there are strong associations with depression, poor quality of life (QoL) and further avoidance of physical activity.11 12 This cycle of activity avoidance only leads to worsening functional ability and there is some evidence to suggest it also leads to an elevated mortality risk independent of disease severity and age.13

    Treatment for patients with IC involves secondary prevention of cardiovascular disease risk, including smoking cessation, diet changes, lipid modification, statin therapy, antiplatelet therapy and management of diabetes and hypertension. In addition to therapeutic intervention and lifestyle modification, the primary treatment to address the functional impairment outlined earlier is for patients to engage in appropriate exercise training, best achieved through a supervised exercise programme (SEP).14 This is supported by multiple consensus guidelines from various governing bodies.15–17,18 However, they lack detail and consistency (between guidelines) as to the appropriate principles of exercise such as intensity and progression (table 1), which impacts upon effective implementation. In addition to inconsistencies in the recommendations for exercise, there is also variability in the delivery of exercise programmes globally with some clinicians reporting lack of expertise or support to guide the exercise delivery.19–21

    View this table:
    Table 1

    Vascular surgery guideline recommendations for exercise

    This guideline for practitioners aims to accompany these consensus guidelines to provide a succinct but more detailed overview of, and recommendations for, exercise prescription and training for IC. While we appreciate that delivery and provision will vary, the key exercise prescription components will remain and as such, this document will be relevant for exercise practitioners worldwide. In addition, we provide advice for the implementation of the exercise prescription guidelines into clinical practice (table 2), which also includes information on structured alternatives when SEPs are not available19 23

    View this table:
    Table 2

    Summary of exercise prescription recommendations

    Walking ability

    Measures of walking ability include pain-free and maximum walking distance (or time) obtained during standardised treadmill testing and/or the distance covered in the 6-min 30-m corridor walk test. Several treadmill protocols have been reported, but the ‘Gardner/Skinner’ incremental protocol is most commonly used.26 27 This involves a constant speed of 3.2 km/hour at a 0% grade, increasing by 2% every 2 min. The advantage of using a treadmill test is that it can be standardised (ie, speed of treadmill, grade of treadmill), although it may not be as reflective of normal everyday walking (6-min walking distance).28 29

    Quality of life

    Several generic and condition-specific questionnaires have been used to assess QoL. The most validated, responsive and reliable questionnaires in the IC population are the Short-Form-36 (SF-36) and King’s College Hospital’s VascuQoL questionnaires, respectively.30 31 Additional and commonly used questionnaires include the Walking Impairment Questionnaire32 and the Peripheral Artery Questionnaire.33

    EXERCISE TRAINING

    Benefits of exercise training

    A recent Cochrane review concluded that there is high-quality evidence showing that SEPs (a variety of regimes) elicit important improvements in both pain-free and maximum walking distance compared with no-exercise control in people with IC.14 A meta-analysis of nine trials (n=391) showed a mean between-group difference in pain-free walking distance at follow-up of 82 m (95% CI 72 to 92 m [follow-up ranging 6 weeks to 2 years]) and maximum walking distance of 120 m (95% CI 50.79 to 190 m). The most commonly tested mode of exercise was walking, with one cycling intervention. The corresponding difference for maximum walking distance was 120 m (95% CI 51 to 190 m; 10 trials, n=500). Improvements of this magnitude are likely to represent clinically meaningful changes in ambulatory function.34

    The same review also reported that there was moderate-quality evidence for improvements in physical and mental aspects of QoL, assessed using the SF-36.14 A meta-analysis of data at 6 months of follow-up showed the physical component summary score to be 2 points higher in exercise versus control (95% CI 1 to 3; 5 trials, n=429). The corresponding difference for the mental component summary score was 4 points (95% CI 3 to 5; 4 trials, n=343). Such differences have the potential to be clinically meaningful.14

    Modes of exercise

    In most studies, SEPs have involved treadmill or track walking at an intensity that elicits moderate to maximal claudication pain.35 There is a strong evidence-base for this type of training, and clinical guidelines cite it as the preferred modality (eg, The Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease II).15 As of 2011, alternate exercise modalities had not been extensively studied.36 In 2005, a randomised trial of 104 participants provided evidence that a 24-week intervention of either cycling or arm-cranking is viable alternatives for improving maximum walking distance (shuttle-walk) up to 29% and 31%, respectively.37 These modalities may be most useful for patients who are unwilling/unable to walk because of severe pain or deconditioning.38 Resistance training may also have a complementary role (eg, for improving muscular strength)39; however, at this point, international guidelines suggest it should not be used as a substitute for aerobic exercise because its impact on walking distance appears modest (eg, McDermott et al 2009). Nevertheless, there is emerging evidence to support its efficacy, and it should no longer be a mode of exercise that is ignored. A recent systematic review and meta-analysis (n=826; 363 resistance trained) demonstrated that resistance training (in comparison to control) can significantly improve both maximum walking distance via constant treadmill testing (standardised mean difference (SMD) 0.51 [95% CI 0.23 to 0.79]) and maximum walking distance via progressive treadmill testing (SMD 0.45 [95% CI 0.08 to 0.83]). Only 6-min claudication onset time (not pain-free treadmill distance) was significantly improved with resistance training (mean difference (MD) 82 m [95% CI 40.91 to 123.54).39

    Frequency of exercise

    A comparison of different training frequencies for patients with IC has not been investigated in a single study. The 1995 meta-analysis of Gardner and Poehlman suggested that an exercise frequency of ≥3 sessions per week was associated with better outcomes compared with <3 times per week, although it should be noted that it pooled data from randomised controlled trials and uncontrolled studies.40 In addition, the 2004 review of Bulmer and Coombes also identified three sessions per week as the optimal frequency for maximum improvements in walking distance.41 Conversely, a meta-analysis in 2012 including 1054 patients did not identify an optimal frequency for programmes.42 The authors of the 2012 meta-analysis do note, however, that a SEP with three sessions per week (in combination with duration of programme and session) ‘would give the best results’.42 Therefore, frequency of SEPs should aim to be at least three times per week, which is in line with common physical activity guidelines for the general population.17

    Duration of programme

    No standardised duration of programme for patients with IC has been identified, with exercise programme length ranging from as little as 2 weeks to as many as 18 months.35 Gardner et al (2012) measured outcomes at 2, 4 and 6 months (n=80) and demonstrated that exercise-mediated improvements in pain-free and maximum walking distances were largely achieved in the first 2 months.43 Additional meta-analysis has also demonstrated that improvements in treadmill walking occur following 3 months of supervised exercise.41 44 45 It may be likely that the optimal prescription is difficult to elucidate due to heterogeneity of studies, including differences in frequency, intensity and type of the exercise. Currently, we recommend that programmes should be at least a minimum of 12 weeks in duration.

    Intensity of exercise

    Exercise intensity is commonly prescribed on the basis of heart rate, rating of perceived exertion, or V̇O2peak obtained via exercise stress testing,46 and may be classified as low, moderate or vigorous based on the American College of Sports Medicine guidelines.47 There is limited information on the appropriate intensities of exercise programmes for patients with PAD.17 48 However, a meta-analysis by Parmenter et al (2015) investigated the relationship between exercise intensity, V̇O2peak (ie, aerobic capacity) and maximal walking distance, and demonstrated that the greatest improvements occurred when exercise intensity was between 70% and 90% HRmax (ie, vigorous according to the American College of Sports Medicine guidelines).49 A further systematic review by Pymer et al (2019) focusing on high-intensity exercise identified four studies that prescribed exercise on the V̇O2peak or HRmax achieved during baseline testing. Overall, six studies demonstrated significant improvements in treadmill maximum walking distances compared with a control group (generally consisting of exercise advice alone).50 However, further research is required to establish the relationship between intensity (moderate vs vigorous) and walking improvements and compare those findings to SEPs.

    Claudication pain scale

    Relatively few trials have used classically defined measures of exercise intensity as described earlier, and for patients with PAD, there is a common misconception between exercise ‘intensity’ and severity of leg pain or discomfort.51 Most reported trials in the literature use the claudication pain scale to instruct patients when to stop exercising and not exercise intensity markers such as heart rate. The claudication pain scale is a continuous scale from 1, indicating no pain, to 5 indicating severe pain,49 with trials often instructing patients to walk to near-maximal pain levels.

    Three studies have specifically investigated the relationship between ‘intensity’ (based on pain) and walking outcomes.52–54 Mika et al (2013) used different intensities corresponding to scores on the pain scale and matched exercise duration in 60 patients.53 Gardner et al (2005) prescribed intensity as ‘high—80%’ or ‘low—40%’ based on the maximal grade achieved at baseline in 31 patients.52 Finally, Novakovic et al (2019) randomised 36 patients to either moderate or pain-free walking, with moderate training prescribed on 70% of the patients predicted HRmax.54 For all studies, outcomes including pain-free and maximum walking distance did not differ between the intensities prescribed. This may highlight that the volume of exercise (and not intensity prescribed) is perhaps the most important factor for improving walking distance in patients with IC.36 49 55 With regard to pain, overall the current evidence seems to favour patients walking near maximal pain for beneficial outcomes. However, walking to no pain, or minimal pain, may also been shown to be effective for this cohort.54 55 Indeed, a meta-analysis by Parmenter et al (2011) showed that walking without inducing claudication pain produced significant improvements in initial claudication distance and also improved absolute claudication distance.36 Additionally, a meta-analysis (six studies) in 2015 demonstrated that improvements in cardiorespiratory fitness were obtained when walking to mild pain (MD 0.79 mL/kg/min [95% CI 0.45 to 1.14]).49 Current recommendations are if patients can tolerate, then walking to moderate pain (i.e 4–5 on the claudication scale) may be suitable. If patients are unable to tolerate higher levels of pain on the claudication scale, then they can walk to low levels of pain, provided the volume of exercise is sufficient,47 which may improve adherence levels.

    Supervision

    Despite consistent evidence demonstrating the clinical effectiveness of SEPs, a European survey conducted in 2012 demonstrated that approximately 30% of the respondents had access to a supervised programme,56 with similar availability in the UK.19 Similar evidence has recently emerged from the USA with 54% of the respondents stating no exercise to a SEP.20 These low provision rates may be attributed to several factors including funding provision, facilities, referral pathways, resources and a lack of trained staff.19 23

    A 2014 review noted uncertainty regarding the benefits of SEPs over unsupervised exercise, especially regarding QoL.51 Despite the apparent superiority of SEPs, there is still a need to develop alternative programmes, given that supervised programmes may be ‘unpopular’ with patients due to financial, time or transport limitations,57 58 or simply because they are looking for a ‘quick fix’.59 As supervised programmes may be unavailable to a large proportion of patients, the development of alternative home-based or ‘self-facilitated’ programmes have been increasingly trialled. These types of interventions have varied in content but include psychological interventions,60 such as cognitive behavioural changes,61 step-monitoring62 and patient education.24

    Home exercise programmes

    Evidence for home-based or self-managed programmes is currently conflicting. In 2013, a systematic review reported that there was low-level evidence to suggest home-based programmes can improve walking distance and QoL in comparison to walking advice or non-exercise.63 In 2018, a Cochrane review including 21 studies and 1400 patients, reported that there was high-quality evidence showing greater improvements in maximum walking distance (measured via treadmill testing) at 3 months among patients enrolled in a SEP versus a home-based programme (95% CI 0.12 to 0.65), or in patients who received walking advice only (95% CI 0.53 to 1.07).64 This translates to walking distance improvements of between 120 and 210 m in favour of supervised exercise, respectively, with similar improvements maintained at 6 and 12 months. However, the prescription of exercise may influence the magnitude of effect, possibly due to training specificity.49 Conversely, the meta-analysis of QoL outcomes showed no marked differences between supervised exercise and home exercise programmes. In a recent randomised trial, McDermott et al (2018) considered the efficacy of home-based exercise (n=99) with wearable technology and telephone coaching versus no exercise advice and found no difference home exercise and control.65 Therefore, further research is required to evaluate the specific components of home-based interventions to maximise patient benefit (ie, wearable technology, on-site visits, etc).

    Safety

    There may be a misconception that exercise training may be unsafe in patients with PAD. Indeed, 70% of the vascular surgeons in one survey thought that cardiovascular comorbidities or aorto-iliac stenosis or occlusions were relative contraindications to exercise.66 Gommans et al (2015) explored the safety of supervised exercise training (via any exercise modality) and reviewed adverse event data from clinical trials.67 Seventy-four trials were included, representing 82 725 hours of training in 2876 patients with a mean age of 64 years (range 54–76 years). Nine adverse events were reported, six of cardiac, two of non-cardiac origin and one fatal adverse event (myocardial infarction). This resulted in an all-cause complication rate of one event per 10 340 patient-hours. The total non-cardiac and cardiac event rate was 1 per 13 788 patients and 1 per 41 363 hours. The study concluded that supervised exercise training is safe for people with IC due to a low all-cause complication rate, and routine cardiac pre-screening is not required.67 However, it should be noted that patients participating in clinical trials might not be a true representation of the overall population. This may be due to strict exclusion/inclusion criteria screening out patients with extensive comorbidities. It would be beneficial to have observational data for adverse events in routine SEPs, to fully elucidate the all-cause complication rates. In addition, it is important to note, that as a patient’s exercise tolerance, pain tolerance and walking ability improve, this may begin to unmask underlying signs and symptoms of coronary artery disease. While not routine practice, cardiac screening may also be considered when patients are engaging in an exercise modality that may not elicit claudication pain such as cycling or when they are engaging in higher-intensity exercise programmes. In general, contraindications to participation in an exercise programme include uncontrolled hypertension, unstable angina or other uncontrolled arrhythmias. Relative contraindications include known obstructive coronary disease, acquired or advance heart block. A comprehensive list of both absolute and relative contraindications can be found in the ‘American College of Sports Medicine Guidelines for Exercise Testing and Prescription’. 47 68

    APPLICATION TO PRACTICE

    Recommendations for exercise training

    All prospective patients should be clinically assessed, and risk stratified to ensure that they do not have any contraindications to the exercise therapy, and to document comorbidities that may need to be accounted for, in order to individualise the exercise programme. Patient ability and preference should also be taken into account when prescribing the exercise programme. Clinical assessment should be repeated as exercise tolerance improves to ensure that the training intensity is sufficient to ensure ongoing patient safety. Any exercise programme should ideally be delivered through an on-site supervised programme with clinical oversight. However, a facilitated, self-managed exercise programme involving behaviour change techniques is a reasonable alternative for patients who prefer this approach or are unable to access supervised exercise.24 The core modality for SEPs should be walking; however, other modes are also efficacious for those who cannot tolerate walking programmes, as outlined in table 2. Alternative modes include arm cranking, cycling, pole-striding and progressive resistance training. A structured programme should involve walking at an intensity that elicits moderate-to-strong claudication pain and should be conducted for a minimum of 3 months, involving at least three sessions of 30–45 min/week. Initial exercise prescription should be based on actual baseline maximum walking distance. Further evidence-based recommendations for exercise training are provided in table 2. However, if patients struggle with the maximum intensity of pain prescribed, then walking at lower pain levels will also lead to improvements in walking ability/distance.36 55

    During exercise training sessions, acute responses to exercise should be monitored to inform the exercise prescription, including heart rate, blood pressure (in the first few exercise sessions), perceived exertion and claudication pain. The continuous monitoring of blood pressure is not recommended but should be revaluated if the intensity or mode of exercise changes. It is recommended that heart rate may be continuously monitored, and blood pressure, perceived exertion and claudication pain are recorded intermittently when the patient stops exercises (if interval walking) or if any signs or symptoms (such as dizziness are present). Finally, programme entry and exit assessments should be performed to determine changes in patient outcomes, including walking distance (primarily 6-min walk test) and QoL.

    To support the provision and uptake of exercise, alongside this guideline an infographic of key messages has been developed that may be used as a poster or handout in clinic; particularly where patients cannot access a supervised programme.69

    SUMMARY

    Exercise training is a safe, effective and low-cost intervention for improving walking ability in patients with IC. Additional benefits may include improvements in QoL, muscle strength and cardiorespiratory fitness. Clinical guidelines advocate supervised exercise training as a primary therapy for IC, with walking as the primary modality. However, evidence is emerging for the role of various other modes of exercise including cycling and progressive resistance training to supplement walking training. In addition, there is emerging evidence for home-based exercise programmes. Revascularisation or drug treatment options should only be considered in patients if exercise training provides insufficient symptomatic relief.

    Summary box

    What is already known?

    • Supervised exercise training promotes clinically meaningful benefit in patients with intermittent claudication.

    • Walking as an exercise modality currently has the strongest level of evidence.

    What this study adds?

    • A concise summary of evidence and practical recommendations for exercise implementation for practioners, including example protocols for exercise training.

    • Progressive resistance training may be used as a supplement to walking programmes.

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    Footnotes

    • Twitter Amy Harwood @AmyHarwood91.

    • Contributors AH, LI, PD, IC and GT were involved in the initial concept of the statement. AH and GT were responsible for the main drafting and editing of the manuscript. All authors provided revisions and critical analysis of the manuscript at each stage of the process and contributed equally to producing and approving the final document.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Ethics approval Not applicable.

    • Provenance and peer review Not commissioned; externally peer reviewed.