The study population was derived from the multicenter REAL-DCB registry (Impact of Drug-Coated Balloon Treatment in De Novo Coronary Lesion; NCT04619277), which includes five teaching hospitals in South Korea: Ulsan University Hospital, Kangwon National University Hospital, Korea University Ansan Hospital, Korea University Guro Hospital, and Ulsan Medical Center. Between October 2010 and December 2023, we retrospectively identified 415 consecutive patients with CKD who underwent successful PCI using a DCB-based strategy, defined as either DCB-only treatment or a provisional hybrid approach with adjunctive DES implantation. The study enrollment process is illustrated in Supplementary Figure 1. Patients were excluded if they had a previous history of coronary artery bypass graft surgery, presented with cardiogenic shock, had severely calcified lesions requiring rotational atherectomy, experienced failed PCI of the target lesion, required long-term oral anticoagulation, or were lost to follow-up.

The comparator group consisted of patients with CKD treated with a DES-only strategy, derived from the Platelet Function and Genotype-Related Long-Term Prognosis in DES-Treated Patients With Coronary Artery Disease (PTRG-DES; NCT04734028) consortium. The design and methodology of the PTRG-DES consortium have been described previously. Briefly, this consortium prospectively collected data from nine registries across 32 academic centers in South Korea between January 2013 and August 2018, enrolling patients treated with second-generation DES. Among 11,226 patients in the overall PTRG-DES cohort, 2,015 had an estimated glomerular filtration rate <60 mL/min/1.73 m². After 1:1 propensity score matching, 415 patients with CKD treated with a DES-only strategy were selected and included in the final analysis. The study protocol was approved by the institutional review boards of all participating centers, and the requirement for written informed consent was waived due to the retrospective nature of the study.

In the DCB-based treatment group, PCI was performed in accordance with current consensus recommendations. ^, DCB-based PCI strategy was defined as an approach in which DCB was considered the default treatment modality, with the final device selection—DCB-only or adjunctive DES implantation—determined by the angiographic results after lesion preparation. DCB was applied when lesion preparation achieved an acceptable result based on consensus criteria, whereas DES implantation was reserved for cases requiring bailout or provisional stenting. This strategy aims to safely reduce overall stent burden while maintaining procedural safety by allowing stenting when necessary. ^, To minimize geographic mismatch, the DCB length was selected to be at least 2 to 3 mm longer on both proximal and distal margins than the predilatation balloon, and balloon inflation was maintained at nominal pressure for a minimum of 60 seconds. When flow-limiting dissections occurred after DCB inflation despite an initially acceptable lesion preparation result, additional PCI with DES implantation was performed. All DCBs used in this study were coated with paclitaxel at a dose density of 3.0 μg/mm² combined with iopromide as a drug carrier. After PCI, DAPT was recommended for 1 to 3 months in stable patients treated with DCB-only PCI and for 6 months in those treated with DES. In patients presenting with acute coronary syndrome, DAPT was recommended for 12 months irrespective of the device used. For procedures involving both DCB and DES, the recommended DAPT duration followed the DES-based strategy.

Patients were followed through scheduled outpatient clinic visits after the index procedure. When in-person follow-up was not feasible, clinical information was obtained through structured telephone interviews. The primary endpoint was the incidence of major bleeding at 2 years. The secondary end point was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, nonfatal MI, stroke, definite target lesion thrombosis, and target vessel revascularization (TVR). Cardiac death was defined as any death not clearly attributed to noncardiac causes, in accordance with established guidelines. MI was defined as a significant elevation of cardiac biomarkers in the presence of ischemic symptoms or objective evidence of myocardial ischemia. Stroke was defined as a new focal neurological deficit lasting ≥24 hours with radiological confirmation; both ischemic and hemorrhagic strokes were included, whereas transient ischemic attacks were excluded. TVR was defined as any clinically driven repeat revascularization, either PCI or coronary artery bypass graft surgery, of the target vessel occurring after discharge from the index hospitalization. Definite target lesion thrombosis was defined according to the criteria of the Academic Research Consortium (ARC)-2, and major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding events. ^,

Categorical variables are presented as counts and percentages, and continuous variables as mean ± standard deviation. Comparisons between groups were performed using the Pearson chi-square test or Fisher’s exact test for categorical variables, and the Student’s t test for continuous variables, as appropriate. Time-to-event clinical outcomes, including major bleeding, MACE and other endpoints, were estimated using the Kaplan–Meier method and compared between groups using the log-rank test.

To adjust for baseline imbalances and reduce the impact of potential confounding, propensity score matching was performed. Propensity scores were estimated using logistic regression incorporating clinical, medication-related, and lesion-related variables, including age, sex, body mass index, hypertension, diabetes mellitus, current smoking, previous MI, previous PCI, previous stroke, end-stage renal disease, clinical presentation, left ventricular ejection fraction, use of aspirin, clopidogrel, statins, beta blockers, calcium channel blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, presence of left main disease, target vessels, lesion characteristics, bifurcation lesions, chronic total occlusion, and multivessel disease. Patients were matched in a 1:1 ratio using nearest-neighbor matching without replacement, with a caliper width of 0.2 of the standard deviation of the logit of the propensity score. The adequacy of matching was assessed using absolute standardized mean differences for each covariate, with values <0.1 indicating negligible imbalance. All p values were two-sided, and a p value <0.05 was considered statistically significant. Statistical analyses performed using R software version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria).