A pooled analysis of the durability and predictors of treatment response of cilostazol in patients with intermittent claudication

Pharmacologic therapy for intermittent claudication in patients with peripheral artery disease (PAD) is limited. We aimed to determine the durability of cilostazol treatment response over time, treatment effects in various subpopulations, and long-term safety. This analysis pooled original data from nine randomized, controlled trials evaluating cilostazol in intermittent claudication, including 1258 subjects treated with cilostazol 100 mg bid. Analysis of covariance was used to compare differences in walking distance, and a pooled random-effects weighted mean difference in maximal walking distance (MWD) was determined. Temporal effects were analyzed by compiling data at 4-week intervals in studies of 24 weeks in duration. Cilostazol was associated with a 50.7% improvement from baseline in MWD compared with placebo (24.3%), with an absolute improvement of 42.1 meters greater than the improvement with placebo (p < 0.001) over a mean follow-up period of 20.4 weeks. Continued increases were demonstrated over the 24-week treatment period. These benefits were seen in all subgroups, after stratifying by age, sex, smoking status, duration of PAD, diabetes, hypertension, prior myocardial infarction, or beta-blocker use. Cilostazol did not increase the risk of all-cause mortality (RR 0.95 [0.68-1.35]). In conclusion, treatment with cilostazol achieves benefits in walking distance that are sustained at 24 weeks and observed irrespective of baseline clinical characteristics. Cilostazol demonstrated no increased risk of all-cause mortality.