Patients with coronary in-stent restenosis (ISR) in multiple stent layers face high recurrence rates and aim to avoid another stent layer. Drug-coated balloons (DCBs) deliver antiproliferative therapy directly to the lesion. The AGENT IDE trial, published in the Journal of the American College of Cardiology, compared a low-dose paclitaxel-coated balloon with an uncoated balloon in patients with multilayer or single-layer ISR.

This prospective, multicenter, randomized trial enrolled 600 patients with ISR in vessels >2.0 mm to ≤4.0 mm and lesion length <26 mm. Patients were randomized 2:1 to paclitaxel-coated or uncoated balloon after lesion preparation, with stratification by ISR type and center. The primary endpoint was 1-year target lesion failure (TLF), defined as ischemia-driven target lesion revascularization (TLR), target vessel-related myocardial infarction (MI), or cardiac death.

Multilayer ISR occurred in 258 patients (44%). At one year, TLF was higher in multilayer than single-layer ISR (29.0% vs 15.7%, P<0.0001). In the multilayer ISR subgroup, the paclitaxel-coated balloon reduced TLF compared with the uncoated balloon (23.8% vs 40.0%; HR 0.55; 95% CI 0.34–0.87; P=0.01), driven by fewer TLR and target vessel-related MI.