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Exercise therapy in intermittent claudication

Exercise therapy is a cornerstone in the management of intermittent claudication; supervised walking exercise three times a week over 12 weeks improves walking ability and quality of life. Despite this, very few patients exercise on a regular basis. The underuse of exercise can be partly explained by lack of available services, and both patients’ and physicians’ lack of interest in exercise. If the goal is to offer best medical therapy to these patients, healthcare professionals must recommend and refer to structured, supervised exercise programmes, which must be made available both in community health services and at the hospitals. In addition, new technology and strategies for facilitating exercise in a home-based setting should emerge.

Peripheral Artery Disease


Background

Peripheral artery disease (PAD) is the third leading cause of atherosclerotic vascular morbidity after coronary heart disease and stroke. More than 200 million people worldwide suffer from PAD, and the numbers are expected to grow due to an ageing population [1]. Furthermore, about 20% of people with PAD have intermittent claudication (IC) [2], that is characterised by cramping, pain or weakness in the leg (or sometimes thigh) muscles during walking. With progression of the disease, the functional level becomes affected, as well as quality of life. Reduced physical activity due to leg pain may lead the patients into a vicious circle, resulting in a sedentary lifestyle, which again increases the risk of progression of atherosclerosis. Daily physical activity can break this circle; however, the patients need support and supervision to achieve a change in lifestyle.

Effects of exercise

Exercise training reduces symptoms in patients by increasing fitness, elevating pain thresholds, improving quality of life and preventing further disease progression [3,4]. A Cochrane review including 1,816 patients with stable leg pain, found that exercise increased maximal walking time by almost five minutes compared with usual care [5]. Pain-free and maximal walking distances increased by 82 and 109 metres, respectively. The improvements lasted for up to two years. The effect of exercise is, however, inconclusive on mortality reduction, cardiovascular events, amputation, and peak exercise calf blood flow [3].

A meta-analysis concluded that quality of life increases with increased walking distance among patients with intermittent claudication [6]. In this context, one study found that exercise vs. surgery produced an equal effect on walking distance, but there were side effects in patients who underwent surgery [7]. These findings were supported by a later meta-analysis that found that training programmes were substantially cheaper and involved fewer risks than either surgery or percutaneous transluminal angioplasty [8]. Another randomised study that compared the effect of physical training and antithrombotic therapy found a significantly greater improvement in walking distance in the exercise group compared with the medication group [9].

The physiological, metabolic, and mechanical alterations that occur during the period of exercise presumably stimulate an adaptive response that ultimately reduces symptoms [10]. Since arterial insufficiency is the primary reason behind intermittent claudication, one may expect that improved symptoms after exercise would be associated with increased blood flow. However, a number of studies have not been able to document increased leg blood flow in patients with improved walking ability [10]. Therefore, it seems likely that changes in microcirculation, endothelial function and oxidative metabolism may explain a large portion of the exercise-induced improvements [10].

Exercise guidelines

In the recently published ESC Guidelines for diagnosis and treatment of peripheral arterial disease, supervised exercise therapy is strongly recommended (IA) in patients with IC, both as primary treatment and after any intervention [4]. This is in line with the American guidelines [11], which give the following recommendations for structured exercise programmes:

  • qualified healthcare providers should supervise the structured exercise programmes in a hospital or outpatient facility 
  • walking exercise is the recommended treatment modality
  • walking should be performed as interval training (walk-rest-walk) at moderate-to-maximum claudication
  • duration of exercise should be at least 30-45 minutes per session, at least three times a week for at least 12 weeks
  • warm-up and cool-down periods should be a part of every session.

Supervised versus unsupervised exercise

Supervised exercise therapy has previously been shown to be statistically significantly effective in improving maximal walking distance or maximal walking time compared to unsupervised exercise [12]. Fourteen randomised trials with 1,002 participants were included in the review. The increase in walking distance was 180 metres in favour of the supervised exercise programmes. However, since participation in supervised exercise programmes is low, focusing on home-based exercise should be emphasised to increase physical activity and adherence to exercise in the long term. There are, however, scarce high-quality data on the effectiveness of home-based supervised exercise to improve symptoms and walking ability in patients with IC. In a review from 2015 [13], only seven randomised controlled trials (along with two non-randomised trials) were identified, comparing home-based supervised exercise with hospital-based exercise or “go home and walk advice”. The authors concluded that home-based supervised exercise may improve maximal and pain-free walking distance compared to just giving advice about exercise, but was less effective than hospital-based supervised exercise. On the other hand, home-based supervised exercise may improve overground walking performance measured with the 6-minute walk test.

Home-based exercise can be supervised by modern technology, for instance using telecoaching or telemonitoring. Wearable activity monitors can be used for goal setting and monitoring, and have been shown to increase physical activity in patients with IC [14]. Telerehabilitation at home, with real-time exercise instruction, is feasible and as equally effective as centre-based rehabilitation in patients with chronic heart failure [15]. In fact, the technology needed to provide supervised home-based exercise already exists. Healthcare professionals just need to be open to introducing it into clinical practice. 

Alternative exercise modes

Even if the recommended exercise mode for claudication is interval walking, patients with IC are often elderly and may have comorbidities that make walking very painful or impossible to perform. There is, however, a growing body of evidence showing that different exercise modes may induce improvements in symptoms and walking ability. A systematic review including 36 randomised controlled trials (32 aerobic with 20 including walking, 4 progressive resistance training [PRT] with 1,183 participants performing exercise) concluded that most modes and intensities of exercise improved walking ability [16]. Both PRT and upper body exercise appeared promising exercise modes; however, additional studies are required to validate their efficacy relative to walking.

Another study assessed whether any exercise mode improved physical fitness and function in patients with IC, and whether improvement in walking ability was related to these outcomes [17]. In this analysis, 24 randomised studies (19 aerobic exercise interventions and 5 PRT) with 924 participants were included. Although data were limited, a strong significant relationship was found between plantar flexor muscle strength and change in pain-free and maximal walking time on a treadmill. Additionally, both walking and PRT significantly improved pain-free and maximal walking distance during a 6-minute walk test.

Safety

Patients with IC are at increased risk of cardiovascular events, and concern about safety during exercise has questioned the need for cardiac screening before entering an exercise programme. In a study by Gommans et al [18], complication rates were reported to be low, with one event per 10,340 patient-hours of exercise. The authors therefore concluded that routine cardiac screening before entering an exercise programme is not required. However, caution should be taken in patients with severe comorbidity.

Future directions

As walking exercise is painful for patients with IC, we believe that alternative and preferably pain-free exercise modes have to be offered as well. Pain-free exercise will be easier to implement in daily life and will probably improve exercise adherence. This requires further research on different exercise modes and exercise intensities, both on efficacy and long-term adherence. Additionally, home-based supervised exercise programmes must be developed and provided using new technology, for instance wearable activity monitors. There is also a need for more data on how exercise and improved fitness and function influence the prognosis in patients with IC.

Conclusion

Supervised walking exercise is a safe and evidence-based treatment in patients with IC, but few patients exercise according to guidelines.

Exercise prevents disease progression, increases fitness, elevates the pain threshold and improves quality of life.

Alternative and less painful exercise modes than walking can improve symptoms and walking ability, and should be further investigated in the future.

Use of new technology needs to be implemented in clinical practice in order to provide supervised home-based exercise for patients with IC.

References


  1. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013 Oct 19;382(9901):1329-40. 
  2. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, McDermott MM, Hiatt WR. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001 Sep 19;286(11):1317-24. 
  3. Pedersen BK, Saltin B. Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports. 2015 Dec;25 Suppl 3:1-72. 
  4. Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Röther J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2017 Aug 26. [Epub ahead of print]. 
  5. Lane R, Ellis B, Watson L, Leng GC. Exercise for intermittent claudication. Cochrane Database Syst Rev. 2014 Jul A18;(7):CD000990. 
  6. Regensteiner JG, Ware JE Jr, McCarthy WJ, Zhang P, Forbes WP, Heckman J, Hiatt WR. Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials. J Am Geriatr Soc. 2002 Dec;50(12):1939-46. 
  7. Lundgren F, Dahllöf AG, Scherstén T, Bylund-Fellenius AC. Muscle enzyme adaptation in patients with peripheral arterial insufficiency: spontaneous adaptation, effect of different treatments and consequences on walking performance. Clin Sci (Lond). 1989 Nov;77(5):485-93. 
  8. de Vries SO, Visser K, de Vries JA, Wong JB, Donaldson MC, Hunink MG. Intermittent claudication: cost-effectiveness of revascularization versus exercise therapy. Radiology. 2002 Jan;222(1):25-36. 
  9. Mannarino E, Pasqualini L, Innocente S, Scricciolo V, Rignanese A, Ciuffetti G. Physical training and antiplatelet treatment in stage II peripheral arterial occlusive disease: alone or combined? Angiology. 1991 Jul;42(7):513-21. 
  10. Stewart KJ, Hiatt WR, Regensteiner JG, Hirsch AT. Exercise training for claudication. N Engl J Med. 2002 Dec 12;347(24):1941-51. 
  11. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017 Mar 21;135(12):e726-e779. 
  12. Fokkenrood HJ, Bendermacher BL, Lauret GJ, Willigendael EM, Prins MH, Teijink JA. Supervised exercise therapy versus non-supervised exercise therapy for intermittent claudication. Cochrane Database Syst Rev. 2013 Aug 23;(8):CD005263. 
  13. Bäck M, Jivegård L, Johansson A, Nordanstig J, Svanberg T, Adania UW, Sjögren P. Home-based supervised exercise versus hospital-based supervised exercise or unsupervised walk advice as treatment for intermittent claudication: a systematic review. J Rehabil Med. 2015 Oct 5;47(9):801-8. 
  14. Normahani P, Kwasnicki R, Bicknell C, Allen L, Jenkins MP, Gibbs R, Cheshire N, Darzi A, Riga C. Wearable Sensor Technology Efficacy in Peripheral Vascular Disease (wSTEP): A Randomized Controlled Trial. Ann Surg. 2017 May 11. [Epub ahead of print]. h
  15. Hwang R, Bruning J, Morris NR, Mandrusiak A, Russell T. Home-based telerehabilitation is not inferior to a centre-based program in patients with chronic heart failure: a randomised trial. J Physiother. 2017 Apr;63(2):101-107. 
  16. Parmenter BJ, Raymond J, Dinnen P, Singh MA. A systematic review of randomized controlled trials: Walking versus alternative exercise prescription as treatment for intermittent claudication. Atherosclerosis. 2011 Sep;218(1):1-12. 
  17. Parmenter BJ, Raymond J, Fiatarone Singh MA. The effect of exercise on fitness and performance-based tests of function in intermittent claudication: a systematic review. Sports Med. 2013 Jun;43(6):513-24. 
  18. Gommans LN, Fokkenrood HJ, van Dalen HC, Scheltinga MR, Teijink JA, Peters RJ. Safety of supervised exercise therapy in patients with intermittent claudication. J Vasc Surg. 2015 Feb;61(2):512-518. 

Notes to editor


Authors:

Inger-Lise Aamot1, Physiotherapist, PhD; Øivind Rognmo2, Exercise physiologist, PhD

  1. Norwegian National Advisory Unit on Exercise Training as Medicine for Cardiopulmonary Conditions, St. Olav’s Hospital, Trondheim University HospitalCardiac Exercise Research Group, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway;
  2. Norwegian National Advisory Unit on Exercise Training as Medicine for Cardiopulmonary Conditions, St. Olav’s Hospital, Trondheim University HospitalCardiac Exercise Research Group, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway

 

Address for correspondence:

Inger-Lise Aamot, Lundåsen 50, 7089 Heimdal, Norway

E-mail: inger.lise.aamot@ntnu.no

 

Author disclosures:

The authors have no conflicts of interest to declare.

 

 

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.