H.J.P Fokkenrood

Innovative strategies for
intermittent claudication

towards a stepped care approach and new outcome measures



Description of the condition

 Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is defined as leg pain in the muscles of the lower extremities that occurs with exercise and is relieved by rest. PAD increases progressively with age, in particular after the age of 40. The relationship between PAD prevalence and age was illustrated by data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES), an ongoing cross-sectional survey of the civilian, non-institutionalized population of the United States. The prevalence of PAD, defined as an ankle-brachial index (ABI; the ratio of blood pressure in the lower legs to blood pressure in the arms) < 0.90 in either leg, was 0.9% between the ages of 40 and 49, 2.5% between the ages of 50 and 59, 4.7% between the ages of 60 and 69, and 14.5% in those 70 years of age and older (Selvin 2004). These numbers indicate that PAD affects more than 5 million adults in the United States. International guidelines reveal 27 million affected individuals in North America and Europe (Norgren 2007).


Description of the intervention

 The primary and most effective treatment for people with IC is exercise therapy (Stewart 2002), which was first suggested by Erb (Erb 1898). In 1966 the first randomized controlled trial (RCT) of exercise therapy in participants with PAD demonstrated an obvious improvement in treadmill walking ability (Larsen 1966). In a Cochrane systematic review of randomized clinical trials, Leng et al (Leng 2000) and later the updated version by Watson et al (Watson 2008) described an overall improvement in maximal walking time: mean difference (MD) 5.12 minutes (95% confidence interval (CI) 4.51 to 5.72) with an overall improvement in walking ability of approximately 50% to 200% associated with exercise therapy compared with no exercise therapy. However, the exercise programs included in this meta-analysis vary widely, ranging from physician recommended unsupervised walking in the com- munity to a formal supervised exercise program involving walking on a treadmill.


How the intervention might work

 Exercise training provides significant symptomatic benefit for patients with claudication; however, the exact mechanisms for this improvement remain unclear (Beckitt 2012). The mechanisms of response to exercise training have been reviewed previously and include improvement in walking efficiency, induction of vascular angiogenesis, inflammatory activation, increased exercise pain tolerance, endothelial and mitochondrial dysfunction, and metabolic adaptations within skeletal muscle (Gustafsson 2001; Hamburg 2011; Norgren 2007; Stewart 2008; Zwierska 2005). Further benefits of exercise therapy are seen in the reduction of cardiovascular risk factors such as hypercholesterolemia, hypertension, and diabetes mellitus. Exercise is therefore implemented in secondary prevention therapies in patients with coronary artery disease (Smith 2011). Given its clear benefits, the importance of exercise therapy is highlighted in contemporary international guidelines (Hirsch 2006; Norgren 2007). In daily practice, lack of specific individual guidance and the absence of uniform supervision appear to be important barriers to the initiation and continuation of exercise therapy (Bartelink 2004).


Why it is important to do this review

 Before the release of the original version of this review in 2006, the prescription of exercise therapy consisted mostly of "go home and walk" advice by the general practitioner, sometimes accompanied by a brochure. After this review was published, more studies compared supervised exercise therapy with non-supervised exercise therapy. Although supervised exercise therapy proved effective in the treatment of PAD by increasing maximal or pain-free walking time or distance, exercise programs are not designed to change day-to-day walking behavior (Crowther 2008; McDermott 2009). Moreover, limitations continue to hinder implementation of supervised exercise programs in daily practice. Some describe the lack of a supervised setting to which patients can be referred to or a lack of knowledge among referring healthcare professionals; in other studies participants are not willing to persist with an exercise program to maintain the benefit (Fokkenrood 2012; Lauret 2012a; Makris 2012; Norgren 2007; Stewart 2008). Therefore debate continues about whether exercise should be offered under supervision. With disregard for all financial and organizational aspects, we believe it is important to provide an accurate systematic review of the effects of supervised exercise therapy in relation to non-supervised exercise on walking distance and quality of life.