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

Abstract

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.

Keywords

• cilostazol
• endovascular revascularization
• exercise therapy
• intermittent claudication
• maximum walking distance
• network meta‐analysis