Prepared by: Dr. Ahmet Caner Canpolat, Dr. Yücel Kanal

Title of the Study: Clinical Outcomes of Bail-out Stenting after Drug-Coated Balloon Angioplasty: The International Multicenter BAILOUT Registry

Presented at: Euro PCR 2025

Link: https://media.pcronline.com/diapos/EuroPCR2025.pdf

Introduction
Percutaneous coronary intervention (PCI) using drug-coated balloons (DCB) is increasingly utilized in the treatment of coronary artery disease, particularly in cases of in-stent restenosis and long/complex lesions. However, due to angiographic deterioration following DCB (i.e., flow-limiting dissection or residual stenosis >30%), some patients require bail-out drug-eluting stent (DES) implantation. The high dose of antiproliferative agents in DCBs may potentially affect the endothelialization of subsequently implanted DES.

Objective
This study aimed to assess whether bail-out DES implantation following DCB-based PCI is non-inferior to a "pre-planned DES-only" strategy.

Methods
This was a retrospective, observational, multicenter registry conducted between 2011 and 2024 across 17 European centers specialized in DCB-PCI. The study included patients who required bail-out DES implantation due to flow-limiting dissection or residual stenosis >30% after DCB treatment. Patients who received bare-metal stents or those who underwent stent implantation prior to DCB were excluded. The primary endpoint was the composite of major adverse cardiovascular events (MACE) at 1-year follow-up, including target lesion revascularization (TLR), cardiac death, myocardial infarction (MI), or stent thrombosis. Statistical analysis tested the safety of the DCB-DES strategy using a pre-specified performance goal of 10.3% MACE and a 3.5% non-inferiority margin. Event rates were calculated using the Kaplan-Meier method, and risk factors were assessed via multivariable Cox regression analysis. Differences between paclitaxel-coated balloon (PCB) and sirolimus-coated balloon (SCB) groups were compared using propensity score-adjusted analysis.

Results
Of the 13,390 patients who underwent DCB-PCI, 733 (5.5%) required bail-out DES implantation and were included in the study. These patients were randomized into PCB (n=386) and SCB (n=347) groups. The mean age was 67.4 years, with 31.7% having diabetes and 20.6% chronic kidney disease. Compared to SCB, the PCB group had a significantly higher rate of acute coronary syndrome (ACS) presentation (44%) and severe calcification (19.2%) (p<0.001), while multivessel disease was more prevalent in the SCB group (51.9%, p<0.001). Lesion characteristics showed a larger reference vessel diameter (RVD) and higher residual stenosis (49.5%) in the PCB group, while in-stent restenosis was more frequent in the SCB group (16.1%). The primary endpoint, 1-year MACE, was observed in 8% of patients, meeting the performance goal and establishing non-inferiority (p<0.001). The stent thrombosis rate was exceptionally low at <1%. Secondary endpoints showed target lesion failure (TLF) at 5.5% and target vessel failure (TVF) at 6.2%. In multivariable analysis, ACS presentation (HR: 1.84), each 1 mm increase in lesion length (HR: 1.02), severe calcification (HR: 2.43), and PCB use (HR: 2.12) were identified as independent risk factors for MACE. Propensity score-adjusted analysis revealed significantly higher risks in the PCB group compared to SCB: MACE (adjusted HR: 2.76), TVF (adjusted HR: 2.64), and MI (adjusted HR: 4.54). These findings suggest that PCB is associated with a higher risk of adverse events compared to SCB.

Conclusion
Bail-out DES implantation following DCB is a safe option with low complication rates (8% MACE) in experienced centers and is non-inferior to a pre-planned DES strategy. However, the observation of higher adverse event rates (MACE, TVF, and MI) in patients treated with PCB compared to SCB highlights a critical point that warrants confirmation through randomized controlled trials. Methodological limitations of the study include its retrospective observational design, the inclusion of only high-volume centers, and the lack of central core laboratory adjudication of events. Additionally, one-quarter of the DCB-PCIs were performed before the publication of the 3rd International DCB Consensus, which standardized the criteria for bail-out stenting. The inclusion of only high-volume DCB-PCI centers may have led to an underestimation of the real-world incidence of bail-out stenting and limited the generalizability of the findings.

Commentary
The BAILOUT Registry demonstrated that bail-out DES following DCB is safe in experienced centers, with low rates of MACE (8%) and stent thrombosis (<1%). However, the increased risk of adverse events observed with PCB compared to SCB may be attributed to the potential negative effects of paclitaxel on endothelial healing. Although the study does not provide details on the drugs eluted by the bail-out DES, it is known that current DES do not contain paclitaxel. Therefore, in cases where bail-out stenting is performed following PCB, the presence of limus-based drugs in the DES may affect endothelialization of the vessel. This hypothesis, however, requires more robust evidence. Moreover, ACS, long lesions, and severe calcification were identified as independent risk factors. While the observational design and the focus on high-volume centers limit the generalizability of the results, the DCB-DES strategy appears to be a safe alternative. Nevertheless, caution is advised when using PCB, and the findings should be further validated through randomized trials.