Paclitaxel-Coated Balloon for the Treatment of Multilayer In-Stent Restenosis

BACKGROUND: Patients with coronary in-stent restenosis (ISR) within multiple layers of stent pose a specific clinical challenge because of higher rates of recurrent restenosis as well as a desire to avoid an additional layer of stent. Drug-coated balloons (DCBs) provide an alternative antiproliferative therapeutic option for multilayer ISR. OBJECTIVES: We evaluated the efficacy and safety of a low-dose paclitaxel-coated vs uncoated balloon among patients with multilayer or single-layer ISR in the AGENT IDE (A Clinical Trial to Assess the Agent Paclitaxel Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis) trial. METHODS: AGENT IDE is a prospective, multicenter trial that randomized patients with ISR (reference vessel diameter >2.0 mm to ≤4.0 mm and lesion length <26 mm) in a 2:1 allocation to paclitaxel-coated or an uncoated balloon following successful lesion preparation. Randomization was stratified by multi- vs single-layer ISR as well as by center. The primary study endpoint was 1-year target lesion failure (TLF): composite occurrence of ischemia-driven target lesion revascularization (TLR), target vessel-related myocardial infarction (MI), or cardiac death. Among patients with multilayer ISR, TLF was lower with paclitaxel-coated balloon compared with an uncoated balloon (23.8% vs 40.0%; HR: 0.55; 95% CI: 0.34-0.87; P = 0.01), driven by reductions in both TLR and target vessel-related MI. Similar findings were observed among patients with single layer ISR (1-year TLF: 13.5% with paclitaxel-coated vs 20.2% with uncoated balloon; HR: 0.64; 95% CI: 0.37-1.11; P = 0.11), although absolute event rates were lower. CONCLUSIONS: Patients with ISR of multiple stent layers had higher rates of adverse stent-related events compared with patients with single-layer ISR. Treatment with a paclitaxel-coated balloon led to greater absolute risk reduction in 1-year TLF among patients with multilayer ISR compared with an uncoated balloon. (A Clinical Trial to Assess the Agent Paclitaxel Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis [ISR] [AGENT IDE]; NCT04647253).