Drug-coated Balloon Angioplasty with Rescue Stenting Versus Intended Stenting for the Treatment of Patients with De Novo Coronary Artery Lesions (REC-CAGEFREE I): an Open-Label, Randomised, Non-Inferiority Trial

Background The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. Methods REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 268%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. Findings Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (693%) of 2272 were male, 698 (307%) were female, and all patients were of Chinese ethnicity. 106 (94%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (64%) of 1133 patients in the DCB group and 38 (34%) of 1139 in the DES group, with a risk difference of 304% in the cumulative event rate (upper boundary of the one-sided 95% CI 452; p(non-inferiority)=065; two-sided 95% CI 127-481; p=00008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (01%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (09%) of 1133 patients in the DCB group and nine (08%) in the DES group. Interpretation In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population.