Impact of Chronic Kidney Disease on Outcomes With Drug‐Coated Balloons Versus Drug‐Eluting Stents: Insights From the REC‐CAGEFREE I Trial

ABSTRACT Background Data regarding the efficacy and safety of drug‐coated balloons (DCBs) versus drug‐eluting stents (DES) in patients with chronic kidney disease (CKD) remains limited. Aims To assess the prognosis of DCB versus DES in patients with and without CKD. Methods REC‐CAGEFREE I was an investigator‐initiated, non‐inferiority trial conducted at 43 sites in China, which randomized 2272 patients to paclitaxel‐coated balloons with the option of rescue stenting (DCB group) or second‐generation sirolimus‐eluting stents (DES group) for treating de novo lesions, regardless of vessel diameter. In this pre‐specified subgroup analysis, patients were stratified based on the presence of CKD (kidney damage or estimated glomerular filtration rate < 60 mL/min per 1.73 m²) at baseline. The primary outcome was the device‐oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically‐indicated target lesion revascularization) at 2 years. Results Of 2272 patients enrolled, 203 (8.9%) had CKD, with 95 and 108 treated with DCB and DES, respectively. At 2 years, the risk of DoCE was significantly higher in CKD versus non‐CKD patients (22/203 [10.9%] vs . 88/2069 [4.3%], HR IPTW : 2.14, 95% CI: 1.13−4.07, p = 0.022). There was no significant interaction between CKD and treatment allocation ( p interaction = 0.352). Among CKD patients, DoCE occurred in 12/95 (12.7%) and 10/108 (9.3%) patients in the DCB and DES groups (HR IPTW : 1.57, 95% CI: 0.66−3.71, p = 0.317), respectively. Among non‐CKD patients, DoCE occurred in 60/1038 (5.8%) versus 28/1031 (2.7%) patients in the DCB and DES groups (HR IPTW : 2.27, 95% CI: 1.38−3.72, p = 0.002), respectively. Conclusion Patients with CKD had worse outcomes compared to those without. DCBs were associated with a higher risk of DoCE than DES, irrespective of CKD status. Trial Registration Unique Identifier: NCT04561739; URL: https://www.clinicaltrials.gov .