Final 2‐Year Results of the REFORM Study: A Randomized Trial of Biolimus DCB Versus Paclitaxel DCB for In‐Stent Restenosis

BACKGROUND: In the REFORM trial, treatment of coronary in-stent restenosis with a Biolimus A9™ drug-coated balloon (BCB) was found to be inferior with respect to in-segment percentage stenosis at 6-months in comparison to treatment with a standard paclitaxel coated paclitaxel-coated balloon (PCB). AIMS: In this manuscript, the final prespecified 2-year clinical follow up follow-up of the REFORM trial is reported. METHODS: The Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the Biolimus A9™ Drug Coated Balloon for the Treatment of In-Stent Restenosis: First-in-Man Trial (REFORM) was a multicenter, single blind, non-inferiority, randomized controlled trial comparing the BCB and PCB in the treatment of coronary in-stent restenosis (ISR). The primary angiographic endpoint of the trial was in-segment % diameter stenosis (%DS) at 6 months, which has previously been reported. A total clinical follow-up duration of 2 years was planned. Prespecified clinical outcomes at 2 years were: target lesion failure (TLF), target vessel failure (TVF), and their individual components. RESULTS: At 24 months, complete follow-up data was available for 93% (n = 188) of the intention to treat (ITT) population. The mean age was 68.7 years, and patients were predominantly male (80.2%). Comorbidities were well balanced between the 2 groups, including diabetes mellitus, which was present in 31% of the BCB group and 29.2% of the PCB group. ISR lesions were predominantly DES-ISR in both groups (BCB 80.7% vs. PCB 85.1%). Through to 2 year follow up, target lesion failure (TLF) occurred in 36 of 135 patients (27.8%) of patients in the BCB group and in 15 of 67 patients (23.5%) in the PCB group (HR: 1.25; 95% CI: 0.69-2.29). Clinically driven target lesion revascularization (CD-TLR) occurred in 31 of 135 patients (24.2%) in the BCB group versus 13 of 67 patients (20.4%) in the PCB group (HR: 1.26; 95% CI: 0.66-2.40). Target vessel myocardial infarction and cardiac death were comparable in both groups. CONCLUSION: In patients with coronary ISR, the final 2-year results from the REFORM study show that TLF rates were 27.8% in the biolimus-coated balloon BCB group and 23.5% in the paclitaxel-coated balloon PCB group. However, given the limited sample size and wide confidence intervals, the present analysis does not permit reliable inference regarding comparative event rates between treatment strategies. The results should be interpreted against the background of demonstrated inferior angiographic performance of the biolimus DCB at 6 months. TRIAL REGISTRATION: The trial was registered prospectively at www. CLINICALTRIALS: gov (identifier: NCT04079192).