Treating multilayer in-stent restenosis (ISR) with a drug-coated balloon (DCB) leads to significantly improved outcomes versus an uncoated balloon in a new analysis of the AGENT IDE trial. Despite better outcomes with a drug coated balloon, those in the study with ISR of multiple stent layers fared worse overall than patients with single-layer ISR. The findings were published Monday online ahead of the August 19 issue of the Journal of the American College of Cardiology, led by Ajay J. Kirtane, MD, from Columbia University Irving Medical Center/NewYork-Presbyterian Hospital and the Cardiovascular Research Foundation, New York. The researchers noted that ISR occurs in approximately 5% of patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in the first year — a rate which increases over subsequent years. In the US, ISR is most commonly treated via balloon angioplasty with the placement of an additional DES, though DCB have recently been approved for ISR based on AGENT IDE findings of superiority over uncoated balloons. Recent European guidelines recommend the use of DES over DCBs for the treatment of ISR, but patients with multi-layer disease pose a “distinct clinical challenge not commonly addressed in clinical guideline recommendations,” the researchers stressed. Specifically, additional layers of stents on top of existing multiple layers is “problematic,” since each new layer further restricts luminal dimensions, they said. “If used after adequate preparation of an ISR lesion, DCBs provide an option to deliver antiproliferative drug to the site of ISR without the need for an additional metal implant that can further compromise luminal area,” the authors added. The current analysis therefore focused on the prespecified AGENT IDE subgroup of patients with multilayer or single-layer ISR to evaluate the safety and efficacy of a low-dose paclitaxel-coated versus uncoated balloon. Of the total 600 patients randomized in AGENT IDE, 258 (44%) had multilayer ISR. At baseline, the single versus multilayer ISR groups had similar mean age, sex weighting (27.3% vs 24.4% female, respectively), body mass index and medical histories, save for significant differences in previous coronary artery bypass graft surgery (24.9% vs 37%, respectively; P = 0.0015) and multivessel coronary artery disease (75.3% vs 83.8%, respectively; P = 0.01). Indication for the procedure were also largely similar between the two groups, including stable angina (54% in single layer ISR vs 54.3% in multilayer ISR; P = 0.94) and non-ST-segment elevation acute coronary syndrome (35.5% vs 39.1%, respectively; P = 0.36). However, silent ischemia was a significantly different reason for the procedure, occurring in more single-layer ISR cases than multilayer (3.2% vs 0.4%; P = 0.01). Multilayer ISR patients overall had higher rates of the 1-year target lesion failure (TLF) primary endpoint compared with patients with single-layer disease (29.0% vs 15.7%; P < 0.0001). When solely comparing multilayer ISR patients, those given DCB had a lower rate of 1-year TLF versus the uncoated balloon group (23.8% vs 40%; hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.34-0.87; P = 0.01). This was driven by reductions in the rates of both target lesion revascularization (17.4% vs 37.8%; HR: 0.40; 95% CI: 0.24-0.67; P = 0.0003) and target-vessel myocardial infarction (5.9% vs 17.2%; HR: 0.33; 95% CI: 0.15-0.74; P = 0.005). For the patients with single layer ISR, absolute event rates were also lower for those given DCB versus uncoated balloon, the researchers added (13.5% vs 20.2%; HR: 0.64’ 95% CI: 0.37-1.11; P = 0.11). In an accompanying editorial, Angelo Oliva, MD, from the Icahn School of Medicine at Mount Sinai, New York, and Humanitas University, Italy, and colleagues, wrote, “these findings underscore both the aggressive nature of multilayer restenosis and the inadequacy of [plain old balloon angioplasty] in this high-risk setting”. They stressed that the study underlines the need for a lifetime management strategy in ISR patients undergoing PCI. “The results support DCBs as a treatment option in high-risk patients with multilayer ISR, offering a chance to improve its otherwise poor prognosis. At the same time, the overall unfavorable outcomes observed in this condition highlight the importance of selecting the optimal strategy at the first ISR occurrence,” wrote the editorialists. They went on to highlight multiple ongoing trials including SELUTION4ISR, MAGICAL-ISR and PREVAIL IDE evaluating newer generation sirolimus- and paclitaxel-based DCBs. “These studies, some of which include patients with multilayer ISR, are expected to provide further insight into the role of DCBs across a broader range of ISR phenotypes,” the editorialists concluded.. Sources: Kirtane AJ, Shlofmitz R, Moses J, et al. Paclitaxel-Coated Balloon for the Treatment of Multilayer In-Stent Restenosis: AGENT IDE Subgroup Analysis. J Am Coll Cardiol; 86: 502-511. Oliva A, Gitto M, Mehran R. Treatment of Multilayer In-Stent Restenosis: Lifetime Management. J Am Coll Cardiol; 86: 512-514. Image Credit: syahrir – stock.adobe.com