BACKGROUND: Endovascular therapy (EVT) with a drug-coated balloon (DCB) is an established treatment for patients with atherosclerotic lesions in the femoropopliteal (FP) artery, including complex lesions. Currently, 3 types of DCBs are available, but the most effective DCB for FP chronic total occlusive (CTO) lesions is unknown. METHODS AND RESULTS: In this retrospective, single-center study, we enrolled 539 consecutive patients (562 FP lesions) treated with EVT between January 2018 and December 2022. Of these patients, 161 with FP CTO lesions who underwent EVT with DCBs were included. Propensity-score matching was performed to compare the clinical outcomes of the high-dose (HD) and low-dose (LD) DCB groups, resulting in the analysis of 56 matched pairs. Primary patency and freedom from target lesion revascularization were significantly higher with HD-DCB than with LD-DCB (89.9% vs. 70.8%, respectively P=0.03
and 93.6% vs. 79.7%, respectively, P=0.046). Multivariate analysis showed that a larger minimum lumen area and the use of HD-DCB (vs. LD-DCB) were favorable predictors of primary patency at 1 year, while a small vessel diameter (≤4.5 mm) was an unfavorable predictor. CONCLUSIONS: For FP CTO lesions, EVT performed with HD-DCB is superior to that with LD-DCB.