Exercise therapy in intermittent claudication

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.