Early Discontinuation of Acetylsalicylic Acid After Angioplasty in Acute Coronary Syndromes: The NEO-MINDSET and TARGET-FIRST Studies

Abstract Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and a P2Y12 receptor inhibitor (P2Y12i) for 12 months represents the standard of care after acute coronary syndrome (ACS). However, balancing ischemic protection against bleeding risk remains challenging, providing the rationale for the development of de-escalation strategies. European and U.S. guidelines allow shortening the duration of DAPT in patients at high bleeding risk, while still maintaining 12 months as the reference recommendation. Interest in abbreviated DAPT regimens has been driven by improvements in percutaneous coronary intervention (PCI) devices and techniques, as well as by a better understanding of the temporal evolution of ischemic and bleeding risks. Several trials have shown that short-duration DAPT followed by monotherapy—particularly with a P2Y12i—is not inferior in terms of ischemic outcomes and significantly reduces bleeding events. In this context, the NEO-MINDSET trial failed to demonstrate the non-inferiority of immediate P2Y12i monotherapy compared with standard DAPT. In contrast, the TARGET-FIRST study confirmed the safety of ASA discontinuation after 30 days in selected patients, with a clear bleeding benefit. Overall, the available evidence indicates that immediate discontinuation of ASA in patients with ACS is not universally safe, whereas strategies based on at least one month of DAPT followed by monotherapy with a potent P2Y12i currently represent the most balanced approach for selected patients. More refined personalization of antiplatelet therapy, guided by an integrated assessment of ischemic and bleeding risks, represents the future perspective in this field.