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Network meta-analysis comparing the outcomes of treatments for intermittent claudication tested in randomized controlled trials [with consumer summary]
Thanigaimani S, Phie J, Sharma C, Wong S, Ibrahim M, Huynh P, Moxon J, Jones R, Golledge J
Journal of the American Heart Association 2021 May 4;10(9):e019672
systematic review

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 4,256 patients were included. At short-term follow-up, home exercise therapy (mean difference (MD) 89.4 m; 95% credible interval (CrI) 20.9 to 157.7), SET (MD 186.8 m; 95% CrI 136.4 to 237.6), and ER+SET (MD 326.3 m; 95% CrI 222.6 to 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 to 318.3) and ER+SET (MD 368.5; 95% CrI 195.3 to 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.

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