Network Meta-Analysis Comparing the Outcomes of Treatments for Intermittent Claudication Tested in Randomized Controlled Trials

Background No network meta-analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short- (<1 year), moderate- (1 to <2 years), and long-term (>= 2 years) follow-up in people with intermittent claudication. Methods and Results A systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health-related quality of life. Network meta-analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty-six trials involving 4256 patients were included. At short-term follow-up, home exercise therapy (mean difference [MD], 89.4 m; 95% credible interval [CrI], 20.9-157.7), SET (MD, 186.8 m; 95% CrI, 136.4-237.6), and ER+SET (MD, 326.3 m; 95% CrI, 222.6-430.6), but not ER (MD, 82.5 m; 95% CrI, -2.4 to 168.2) and cilostazol (MD, 71.1 m; 95% CrI, -24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate-term follow-up, SET (MD, 201.1; 95% CrI, 89.8-318.3) and ER+SET (MD, 368.5; 95% CrI, 195.3-546.9), but not home exercise therapy (MD, 99.4; 95% CrI, -174.0 to 374.9) or ER (MD, 84.2; 95% CrI, -35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long-term follow-up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta-analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively. Conclusions This network meta-analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term (<2 year) but not beyond this. Durable treatments for intermittent claudication are needed.