Effects of exercise prescribed at different levels of claudication pain on walking performance in patients with intermittent claudication: a protocol for a randomised controlled trial.

BACKGROUND: Peripheral artery disease affects over 236 million people globally and the classic symptom is intermittent claudication (IC) which is associated with reduction in physical activity. The evidence that supervised exercise programmes (SEPs) improve pain-free and maximal walking distance is irrefutable. However, adherence rates are low with exercise-related pain cited as a contributing factor. National and international guidelines recommend exercising at a moderate to maximal level of claudication pain to improve walking ability; however, exercising pain-free or at mild claudication pain has been shown to achieve this outcome. There is limited evidence that compares the relative effects of exercise prescribed at different levels of claudication pain. OBJECTIVE: The objective of this study is to directly compare the effects of exercise prescribed at three different levels of claudication pain on walking performance. DESIGN: This study will be a single-centre randomised controlled trial. METHODS: Based on an a priori power calculation, 51 patients with IC will be allocated to 24 weeks of twice-weekly pain-free (PF), moderate pain (MOD-P) or maximal pain (MAX-P) exercise. The PF group will cease exercise at the onset of claudication (1 on the 0-4 IC rating scale), the MOD-P group will stop once moderate pain is reached (2 on the rating scale) and the MAX-P group will stop once maximal pain is reached (4 on the rating scale). ANALYSIS: Outcome measures will be assessed at baseline, 12 and 24 weeks adopting an analysis of covariance (ANCOVA) to compare MWD across three time points. The primary outcome for the trial will be change in maximal treadmill walking distance at 12 and 24 weeks. REGISTRATION: Trial registration number: NCT04370327.

A Systematic Review of Exercise Prescription in Patients with Intermittent Claudication: Does Pain Matter?

BACKGROUND: Current guidelines for intermittent claudication advocate exercise at moderate to maximal claudication pain. However, adherence rates to supervised exercise programmes (SEP) remain poor and claudication pain is a contributing factor. Limited evidence suggests that moderate or pain-free exercise may be just as beneficial and may be better tolerated. However, it remains unclear what 'level' of claudication pain is optimal for improving functional outcomes. We therefore conducted a systematic review to synthesise the evidence for exercise prescribed at different levels of claudication pain. METHODS: The CENTRAL, MEDLINE, Embase and CINAHL databases were searched up to October 2020. Randomized controlled trials (RCTs) that directly compared at least 2 different intensities of claudication pain were included. Outcome measures included walking performance, adherence, quality of life and vascular function. RESULTS: Of 1,543 search results, 2 studies were included. Maximal walking distance improved by 100-128% in the moderate-pain SEP groups, and by 77-90% in the pain-free SEP groups. Importantly, there were no significant differences between the moderate-pain and pain-free SEP groups in either study for improvements in walking performance, though comparison to a maximal-pain SEP group was not made. CONCLUSIONS: The efficacy of SEPs for patients with intermittent claudication is irrefutable, though there is no consensus on the optimal level of pain. Therefore, adequately powered RCTs are required to compare the effect of pain-free SEPs, moderate-pain SEPs and maximal-pain SEPs on functional outcomes. (PROSPERO ID: CRD42020213684).

The severity of muscle ischemia during intermittent claudication.

PURPOSE: The degree of ischemia during intermittent claudication is difficult to quantify. We evaluated calf muscle ischemia during exercise in patients with claudication with near infrared spectroscopy. METHODS: A Critikon Cerebral Redox Model 2001 (Johnson & Johnson Medical, Newport, Gwent, United Kingdom) was used to measure calf muscle deoxygenated hemoglobin (HHb), oxygenated hemoglobin (O(2)Hb), and total hemoglobin levels and oxygenation index (HbD; HbD = O(2)Hb - HHb) in 16 patients with claudication and in 14 control subjects before, during, and after walking on a treadmill for 1 minute (submaximal exercise). These measures were repeated after a second maximal exercise in patients with claudication and after 7 minutes walking in control subjects. Near-infrared spectroscopy readings during maximal exercise were then compared with a model of total ischemia induced with tourniquet in 16 young control subjects. RESULTS: Total hemoglobin level changed little during exercise in both patients with claudication and control subjects. HHb levels rose, and O(2)Hb level and HbD falls were more pronounced in patients with claudication than in control subjects after submaximal and maximal exercise. During maximal exercise, HbD fell markedly by a median (interquartile range) of 210.5 micromol/cm (108.2 to 337.0 micromol/cm) in patients with claudication compared with 66.0 micromol/cm (44.0 to 101.0 micromol/cm) in elderly control subjects and 41.0 micromol/cm (36.0 to 65.0 micromol/cm) in young control subjects (P <.001). This fall also was greater than the HbD fall induced with tourniquet ischemia at 90.8 micromol/cm (57.6 to 126.2 micromol/cm; P =.006). CONCLUSION: Hemoglobin desaturation in exercising calf muscle is profound in patients with claudication, considerably greater even than that induced with three minutes of tourniquet occlusion. Further studies are necessary to investigate the relationship between the inflammatory response and near-infrared spectroscopy during exercise in patients with claudication.