Impact of Circumferential Calcification and Acquired Minimum Lumen Area on 1‐Year Primary Patency After Drug‐Coated Balloon Angioplasty for Femoropopliteal Lesions

ABSTRACT Background Severe calcification predicts restenosis after drug‐coated balloon (DCB) angioplasty for femoropopliteal lesions, but whether an adequate post‐procedural minimum lumen area (MLA) can attenuate this effect, and how intravascular ultrasound (IVUS) circumferential calcification compares with angiographic Peripheral Arterial Calcium Scoring System (PACSS), remain unclear. Methods In this exploratory sub‐analysis of the multicenter REAL‐LEAD registry, we studied 224 femoropopliteal lesions (222 analyzable) treated with a DCB‐only strategy under IVUS guidance across 14 Japanese institutions, classified by IVUS calcification angle (≥ 180° vs. < 180°) and PACSS grade (3–4 vs. 0–2). Cox models assessed 1‐year loss of patency; post‐procedural MLA was modeled continuously. Results Restenosis occurred in 37 lesions (16.7%) over 1 year. An IVUS calcification angle ≥ 180° independently predicted loss of patency (HR 2.17, 95% CI 1.10–4.26, p = 0.025); PACSS grade 3–4 did not retain significance after identical adjustment (HR 1.79, 95% CI 0.91–3.54, p = 0.092). Each 1.0 mm 2 decrease in MLA increased restenosis hazard by 32% (HR 1.32, 95% CI 1.19–1.47, p < 0.001). Despite comparable external elastic membrane area at the MLA site ( p = 0.67), severely calcified lesions acquired a smaller MLA. Severely calcified lesions with an adequate MLA achieved 1‐year patency (90.6%) approaching that of low‐calcification lesions with an adequate MLA (94.7%), while low‐calcification lesions with an inadequate MLA fared worse (73.4%). Conclusions IVUS‐defined circumferential calcification, but not angiographic PACSS, independently predicted restenosis after DCB‐only angioplasty. An adequate post‐procedural MLA appeared to attenuate the adverse impact of severe calcification, supporting IVUS‐guided optimization of acute luminal gain as an actionable procedural target.