Drug-coated balloon (DCB) was found to be non-inferior to drug-eluting stent (DES) for treating de novo lesions in patients with acute coronary syndrome (ACS) in terms of fractional flow reserve (FFR) at 9 months, according to the DCB-ACS trial. These findings were presented by Haibo Jia, MD, PhD, of the Second Affiliated Hospital of Harbin Medical University, China, as late-breaking science Thursday at the Transcatheter Cardiovascular Therapeutics (TCT) 2023 conference in San Francisco. ACS is one of the leading causes of mortality worldwide. DES are the standard therapy for interventional treatment of ACS. DCB is a potential therapeutic strategy of choice in ACS. However, there is limited evidence for DCB treatment in ACS patients with de novo lesions. The DCB-ACS trial, a randomized, multicenter trial conducted in China, aimed to determine whether the DCB was noninferior to the DES in ACS patients. Between April 19 and November 18, 2021, 224 patients from 15 medical centers in China were enrolled and randomized, and 216 patients were included in the final analysis. The DCB group had 107 patients and the DES group included 109 patients. The primary endpoint was a physiology measure, FFR assessment of the target lesion at 9 months. Secondary outcomes were target lesion failure (TLF) and a patient-oriented composite endpoint (POCE). At baseline, the patients’ mean age was 59.0 ± 9.5 years and most (73.2%) were male. The results demonstrated that the DCB-only strategy was non-inferior to DES for treating de novo lesions in ACS patients in terms of FFR at 9 months. The mean lesion level FFR value was 0.89 in the DCB group and 0.90 in the DES group, with a mean difference of -0.011 (95% confidence interval: 0.036-0.015). The lower bound of the 95% confidence interval of the mean difference, -0.036, was greater than the prespecified noninferiority margin, -0.05 (p-noninferiority = 0.001). Additionally, there were no significant difference between the two groups in terms of TLF and POCE at 12-month follow-up. Jia showed a slide of 42-year-old male who presented with STEMI and was treated with DCB for a left anterior descending artery lesion. At 9-month follow up, the FFR of the lesion was 0.89. The optical coherence tomography (OCT) images of the lesion at baseline and at 9 months showed significantly satisfying results. Despite the small size and highly selective nature of the DCB-ACS study population, it highlights that DCB can be a viable treatment option for ACS patients. Large randomized clinical trials to further evaluate the safety and efficacy of DCB in comparison with DES. Photo Caption: Haibo Jia, MD, PhD, speaks during a news conference Thursday at the Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco. Photo Credit: Jason Wermers/CRTonline.org