P2Y12 inhibitor monotherapy is not noninferior to dual-antiplatelet therapy (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS), according to final results from the NEO-MINDSET trial. Pedra A. Lemos, MD, PhD, of the Hospital Israelita Albert Einstein, Sau Paulo, Brazil, presented these data during a Hot Line session on Sunday at the European Society of Cardiology (ESC) Congress 2025 in Madrid. Results were also simultaneously published online in The Lancet on Sunday. “We failed to demonstrate the noninferiority of aspirin-free monotherapy initiated immediately after PCI with regard to the ischaemic primary endpoint over 12 months,” Dr. Lemos said during an ESC news release on Sunday. While a combination of DAPT, aspirin plus a P2Y12 inhibitor is a standard management strategy for 12 months post-PCI for patients with ACS, this practice increases patients’ risk of bleeding events. Most of these bleeding complications happen within a short window after PCI. The investigators in this study examined the use of P2Y12 inhibitor monotherapy immediately post-PCI without aspirin compared with the standard treatment regimen of DAPT, aspirin and P2y12 inhibitors. NEO-MINDSET (Percutaneous Coronary Intervention Followed by Monotherapy Instead of Dual Antiplatelet Therapy in the Setting of Acute Coronary Syndromes) was a multicenter, open-label, randomized trial that took place in Brazil. A composite of all-cause mortality, myocardial infarction, stroke or urgent target-vessel revascularization, as well as major or clinically relevant nonmajor bleeding, were the 2 ranked primary outcomes. The composite was tested for noninferiority and the bleeding endpoint was tested for superiority in the trial. A total of 3,410 patients were randomized to receive either the DAPT regimen (n=1,698) or P2Y12 monotherapy (n=1,712). In the monotherapy group, the composite primary endpoint occurred in 119 patients. This occurred in 93 patients in the DAPT group (absolute risk difference=1.45, 95% confidence interval [CI]: -0.16 to 3.10, p for noninferiority=0.11). Major or clinically relevant nonmajor bleeding took place in 33 monotherapy patients and 82 DAPT patients (absolute risk difference: -2.97, 95% CI: -4.20 to –1.73). In the monotherapy group, 12 patients experienced stent thrombosis, while only 4 DAPT patients experienced stent thrombosis. Overall, P2Y12 inhibitor monotherapy was not noninferior to the standard DAPT regimen in patients with ACS who underwent PCI. “Results from the landmark analysis suggest that the excess ischaemic risk with monotherapy occurred in the first 30 days, with comparable outcomes thereafter. Bleeding appeared to be lower at both 30 days and 12 months with monotherapy vs. DAPT,” Dr. Lemos concluded in the news release. Source: Guimarães PO, Franken M, Tavares CM, et al. Early withdrawal of aspirin after PCI in acute coronary syndromes. Lancet. 2025 August 31 (Article in press). This trial was funded by the Brazilian Ministry of Health. Image Credit: European Society of Cardiology (ESC) Congress 2025 Press Office. Image Caption: Pedra A. Lemos, MD, PhD, discusses the NEO-MINDSET trial during a Press Conference at the European Society of Cardiology (ESC) Congress 2025.