Drug-coated balloons (DCBs) demonstrated noninferiority to drug-eluting stents (DES) in treating de novo lesions in small coronary vessels in a new meta-analysis of randomized controlled trials. Bernardo Cortese, MD, of Fondazione Ricerca e Innovazione Cardiovascolare, Milan, presented these results from the ANDROMEDA study during a Late-Breaking Clinical Trials session Saturday at Cardiovascular Research Technologies (CRT) 2024 in Washington, D.C. ANDROMEDA is a meta-analysis of randomized controlled trials comparing DCB with DES as treatment for de novo lesions with at least 3-year follow-up. Four trials were included: BELLO, PICCOLETO II, BASKET SMALL 2 and RESTORE SVD, with a total of 1,145 patients. The investigators searched four electronic databases – PubMed, Scopus, Science Direct, Web of Science – and archives of major scientific societies and international conferences dating from May 2010, which is when the first randomized clinical trial evaluating treatment of de novo lesions in small vessels with DCB, to January 2024. The primary investigator of each included trial was invited to participate in the study, and additional unpublished data for each trial were used when available. The primary endpoint was the hierarchical composite of major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction (MI), target lesion revascularization, or acute vessel occlusion. The study also included a landmark analysis at 12 months. The analysis included 1,154 patients, with 582 in the DCB arm and 572 in the DES arm. The patients’ median age was 67 years (interquartile range [IQR]: 60-75), and about a quarter (24.2%) of the patients were female. Most patients presented with silent ischemia or stable angina (71.2%), and three-quarters (76.6%) had multivessel disease. The DCB arm had a slightly lower percentage of female patients (21.8%) than the DES arm (26.6%), and the DCB group was numerically younger (median age 66 [IQR: 59-74]) than the DES group (median age 68 years [IQR: 61-75]). In the intention-to-treat analysis, the incidence of MACE at 3 years was significantly lower in the DCB arm (15.8% vs. 24.5%; hazard ratio [HR]: 0.67; 95% CI: 0.47-0.96; p=0.027). This result was driven by MI (4.7% vs. 7.8%; HR: 0.57; 95% CI: 0.35-0.94; p=0.028). There was no significant difference between DCB and DES in target lesion failure (14.7% vs. 17.6%; HR: 0.78; 95% CI: 0.55-1.12; p=0.184) at 4 years. Study limitations included that there might be significant differences for some baseline angiographic characteristics between the group because BASKET-SMALL 2 included vessels up to 3 mm in diameter, while PICCOLETO II and BELLO limited vessel size to 2.75 mm or smaller. Also, the PICCOLETO II and BELLO trials incorporated planned angiographic follow-up as part of the study protocol, which has the advantage of adding information about the mechanisms of recurrent target lesion failure but has the potential disadvantage of influencing the natural clinical course of events (i.e., more TLR or MIs). Finally, the trials used differing definitions of MI. Cortese noted that DCBs have recently emerged as an alternative to DES as treatment for de novo lesions in small coronary arteries. He added that DCBs have emerged to show a reduction in late adverse clinical events in comparison with DES, as shown in the ANDROMEDA meta-analysis, and that the events were mainly driven by a reduction in acute MI, stent thrombosis and TLR at 3 years with DCBs. Ongoing clinical trials, including TRANSFORM II and SELUTION, will add more information concerning the role of DCBs in larger patient populations, he added. Photo Credit: Jason Wermers/CRTonline.org Photo Caption: Bernardo Cortese, MD, presents findings from the ANDROMEDA study Saturday at CRT 2024 in Washington, D.C.