Identifying the Most Clinically Effective Exercise Prescription for Improving Maximum Walking Distance in People with Intermittent Claudication (MAXIMISE): A Systematic Review with Network and Component Network Meta-analysis

OBJECTIVE: Supervised exercise programmes are first line treatment for patients with intermittent claudication. Their prescription comprises a combination of components, namely frequency, intensity, time, and type of exercise. However, the optimal prescription (i.e., the most effective combination of these components) remains unknown. This leads to a paucity of comprehensive programme guidelines, poor programme provision, uptake, and completion rates, and potentially ineffective programmes. The aim of this systematic review with network and component network meta-analyses was to identify evidence for the optimal supervised exercise prescription for patients with intermittent claudication. DATA SOURCES: CENTRAL, MEDLINE, Embase, CINAHL, trial registries, and Web of Science. REVIEW METHODS: Randomised controlled trials of patients with intermittent claudication comparing a supervised exercise programme with an appropriate, non-invasive comparator group, or another alternative supervised exercise programme were included. The primary outcome was mean difference in maximum walking distance between the exercise and control groups. A component network meta-analysis was planned to identify the most effective combination of components. However, the assumption required for a valid component network meta-analysis was violated, requiring alternative primary analyses. This involved initially grouping trials by their common components and undertaking standard network meta-analyses for each group to identify the likely effective levels (e.g., once or twice per week). These results were supported by other analyses to identify a likely optimal prescription. RESULTS: Searches returned 13 714 unique results. Sixty four trials (n = 3 427) were included in the primary analysis. The likely optimal supervised exercise prescription is intermittent walking, performed three times a week, using a pain based prescription (ranging from pain free or pain onset to maximum pain) for 30 - 60 minutes per session, for a period of 12 weeks (moderate to high quality evidence). CONCLUSION: This study identified the likely optimal supervised exercise prescription for patients with intermittent claudication, which should inform future guidelines, clinical practice, and clinical trials.