Treating patients with multilayer in-stent restenosis (ISR) with a paclitaxel-coated balloon was associated with reduced risk of target lesion failure (TLF) at one year vs. an uncoated balloon, according to a subgroup analysis of the AGENT IDE trial published Aug. 11 in JACC.

Ajay J. Kirtane, MD, SM, FACC, et al., included 600 participants (44% with multilayer ISR) from the prospective, multicenter trial, investigating the safety and efficacy of using a low-dose paclitaxel-coated vs. uncoated balloon to treat patients with multilayer or single-layer ISR. The primary endpoint was TLF – composite occurrence of ischemia-driven target lesion revascularization (TLR), target vessel-related myocardial infarction (MI), or cardiac death – at one year.

Overall, patients with multilayer ISR exhibited higher rates of TLF at one year vs. those with single-layer ISR (29% vs. 16%, p<0.0001). Patients with multilayer ISR had lower rates of TLF when treated with the paclitaxel-coated balloon as opposed to an uncoated balloon (24% vs. 40%; hazard ratio [HR]: 0.55; 95% CI: 0.34-0.87; p=0.01). Reductions in TLR and target vessel-related MI were primarily responsible for the differences in TLF.

Although absolute event rates were lower among patients with single-layer ISR, the authors note similar results when comparing the paclitaxel-coated vs. uncoated balloon (14% vs. 20%; HR: 0.64; 95% CI: 0.37-1.11; p=0.11).

Stent thrombosis occurred in six patients with multilayer ISR, all of whom were part of the uncoated balloon arm of the trial. "The asymmetry in risk of stent thrombosis between treatment groups is notable ([drug-coated balloon]: 0 vs. control: 6), although this trial was underpowered to assess such low-frequency events definitively," note the authors. "Further, three of the six stent thrombosis events occurred following a TLR event, further emphasizing the recurrent and longitudinal nature of stent failure in multilayer ISR."

"The overall unfavorable outcomes observed in this condition highlight the importance of selecting the optimal strategy at the first ISR occurrence," add Angelo Oliva, MD; Mauro Gitto, MD; and Roxana Mehran, MD, FACC, in an accompanying editorial comment. "Although [drug-eluting stent] implantation may provide better acute outcomes than [drug-coated balloon] angioplasty, adding another stent layer increases the risk of future multilayer ISR and its complications."