Background: 

• 10% of PCIs are for coronary in-stent restenosis (ISR), and effectively treating ISR without adding another layer of stent is desirable. 

• Using a Paclitaxel-Coated Balloon (DCB) may avoid another layer of stent placement, and shorten the need dual antiplatelet therapy (DAPT) duration to one month. 

• The AGENT IDE trial is a pivotal, multicenter, randomized controlled trial, evaluating the safety and efficacy of AGENT DCB versus an uncoated balloon in ISR patients. 

• The FDA approved AGENT DCB based on the primary data from the AGENT IDE trial, and the 2-year follow-up data is now being presented at CRT 2025. 

Methods: 

• Patients with ISR in a previously stented lesion (lesion size 2-4 mm and length <26 mm) were randomized to receive either AGENT DCB (N=406) or an uncoated balloon (N=194). 

• Exclusions included patients with recent MI, renal insufficiency, low EF, unprotected left main disease, target lesions in grafts, or thrombus. 

• 43% of the cases had multilayer ISR, and around two-thirds of patients in each group underwent PCI with intravascular imaging guidance. 

Results: 

• Primary Endpoint: Target Lesion Failure (TLF) occurred in 27% of the AGENT DCB group vs 34% in the uncoated balloon group, with a statistically significant difference (P=0.04). 

• Secondary Outcomes: There was no significant difference between the groups for all-cause death, cardiac death, or myocardial infarction (MI). 

Conclusion: 

• The AGENT DCB was found to have superior outcomes in treating ISR compared to the uncoated balloon, in line with previous results from the AGENT IDE trial. 

• However, the trial did not compare DCB to drug-eluting stents (DES), which remains the standard treatment for ISR. 

Takeaway Messages: 

• AGENT DCB holds promise as an alternative to DES for treating ISR and has shown better outcomes compared to uncoated balloons. 
• The long-term safety of DCB compared to DES remains unclear, as randomized data on this comparison is lacking. 
• A potential subgroup that could benefit from DCB are those with multilayer ISR, where adding another stent layer might not be ideal. 

This trial highlights a significant step forward in ISR management by providing an effective alternative to placing additional stents. The key challenge remains understanding the long-term safety and effectiveness of DCB compared to the well-established DES, especially in the context of complex ISR cases.