SAN FRANCISCO – First and recurrent revascularizations may be reduced with the use of drug-coated balloons (DCBs) or drug-eluting stents (DES) rather than balloon angioplasty, a secondary analysis of the ISAR-DESIRE 3 trial shows. More than10 years after initial percutaneous treatment of DES in-stent restenosis (ISR) lesions, patients continue to have a high rate of repeat target lesion revascularization (R-TLR), according to the trial. Tobias Koch, MD, of the Technische Universität München, Munich, Germany, presented these results during a late-breaking clinical science session Thursday at Transcatheter Cardiovascular Therapeutics (TCT) 2023. A manuscript reporting these results was simultaneously published online in JACC: Cardiovascular Interventions. Treatment of coronary artery disease is frequently limited by ISR. About 5% to 10% of patients post-DES implantation will experience DES-ISR. There are currently slim guidelines for interventional cardiologists regarding recurrent ISR, and long-term safety and efficacy outcomes, with the newly available treatment strategies, have not been investigated in this population. The ISAR-DESIRE 3 trial randomized 402 patients with 500 lesions between August 2009 and October 2011 across three German centers. The current study is a post hoc, prospective, open-label, randomized analysis. Patients received plain balloon (PB), DCB (SeQuent Please; B. Braun) or DES (Taxus Liberté; Boston Scientific) to treat ISR. The primary endpoint of this secondary study was first or recurrent ISR after randomization during index PCI followed by R-TLR by any repeat PCI or coronary artery bypass graft surgery. The median follow-up time was 10.3 years. A total of 204 lesions needed first R-TLR by the end of follow-up: 82 in the PB group, 70 in the DCB patients and 52 in the DES group. The R-TLR total was 373 (PB=162, DCB=124, DES=87). Through the 1-year follow-up, DCB reduced the total risk of R-TLR (hazard ratio [HR]=0.36; 95% confidence interval [CI]=0.24-0.54) as did DES (HR=0.36; 95% CI=0.14-0.38). DCB numerically, non-significantly reduced the number of 1-year follow-up R-TLRs (HR=0.77; 95% CI=0.51-1.16) while DES significantly reduced the number of R-TLRs (HR=0.61; 95% CI=0.39-0.95), compared with PB. Cardiovascular risks were similar between the DCB and DES groups during (HR=1.54; 95% CI=0.89-2.69) and post-1-year follow-up (HR=1.26;). Some limitations of this study include the post hoc design, it may not be generalizable to non-target-lesion populations, and the total revascularization event analysis was not included in the study protocol. Efficacy within the treatment strategies should also be considered with caution because patients underwent R-TLR with other treatment strategies in consideration of further events. Roxana Mehran, MD, of the Mount Sinai School of Medicine, the moderator of the TCT news conference Thursday, expressed her concerns about the availability of these procedures in the U.S. “The fact that 10 years ago, drug-coated balloons were available in Europe and in fact, in 2014, in the European Society of Cardiology, the class I indication for ISR, that we still here in the United States don’t have it available, is really problematic,” Mehran said. Overall, DCB, especially DES, reduced the number of primary and persistent revascularizations, compared with PB, in patients receiving DES-ISR treatment. In an accompanying editorial, Ron Waksman, MD, and Kaylan R. Chitturi, DO, of MedStar Washington Hospital Center, Washington, D.C., discussed advances in stent technologies and the differences between them, as well as common misunderstandings about DES-ISR. Both the editorialists and the news conference panelists commended the investigators of this study for collecting data over an entire decade. However, all commenters noted several limitations of the study. “You should be congratulated on a very elegant study design, 10-year outcomes are very valuable,” said Yousif Ahmad, BMedSci, BMBS, MRCP, PhD, of the Yale University School of Medicine, during the news conference, “DES are effective in restenosis...but it keeps things unlocked [for patients] in the future.” “[The investigators’] achievement in collecting clinical follow-up data for up to 10 years is extremely rare. However, this study has some limitations that leave uncertainty regarding the interpretation of results and conclusions,” the editorialists wrote. Waksman and Chitturi suggested potential management for usage of DES-ISR to reduce the use of stents in high-risk patients, such as diabetic patients or those small-vessels or bifurcation lesions, and described how this study contributes to the growing need for research in this field. The editorialists concluded, “This study dispels the myths that POBA [plain old balloon angioplasty] is effective for DES-ISR, and that implantation of another DES is harmful and should be avoided.” Sources: Koch T, Lenz T, Rheude T, et al. Recurrent Revascularization at 10 Years after Percutaneous Treatment of Drug-Eluting Stent Restenosis. JACC Cardiovasc Interv. 2023 Oct 26 (Article in Press). Waksman R, Chitturi KR, Myths and Truths in the Management of Drug-Eluting Stent In-Stent Restenosis. JACC: Cardiovasc Interv. 2023 Oct 26 (Article in Press). Photo Caption: Tobias Koch, MD, , speaks during a news conference Thursday at the Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco. Photo Credit: Bailey Salimes/CRTonline.org