November 20, 2025Journal of the American College of Cardiology
Potent P2Y12 Inhibitor Monotherapy vs DAPT After PCI in Patients With and Without STEMI
Caio A.M. TavaresPatrícia O. GuimarãesMarcelo FrankenJosé MarianiStefano Garzón Dias LemosBreno Oliveira AlmeidaEduardo B. MartinsEstêvão Lanna FigueiredoAlexandre SoaresMarcos Maynar-MariñoBruno PaolinoMayler Olombrada Nunes de SantosPaulo CaramoriRodrigo M JoaquimEdgar Freitas QuintellaAndré F AntonangeloMarcos S. SilveiraFrederico MonfardiniSilvia R.L. AssisJosé Carlos NicolauAndrei C. SpósitoYoshinobu OnumaMarco ValgimigliDominick J. AngiolilloPatrick W. SerruysOtávio BerwangerRaúl D. SantosFernando BacalPedro A. Lemos
Key result
Early potent P2Y12 monotherapy increases STEMI ischemic events ~60% vs DAPT but reduces overall bleeding.
- HR 1.60
- 95% CI 1.14-2.24
- n=3,410
Journal of the American College of Cardiology published a graphical abstract
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Why the study?
The effects of very early aspirin withdrawal with potent P2Y12 inhibitor monotherapy after PCI may differ based on ACS presentation (STEMI vs NSTE-ACS).
Does potent P2Y12 inhibitor monotherapy reduce ischemic and bleeding events compared to DAPT in patients with ACS treated with PCI?
Key Points
- To evaluate whether the efficacy and safety of early aspirin discontinuation followed by potent P2Y12 inhibitor monotherapy differ between STEMI and NSTE-ACS patients undergoing PCI.
- Prespecified subgroup analysis of the randomized NEO-MINDSET trial (NCT04360720) including 3,410 ACS patients (2,119 STEMI and 1,291 NSTE-ACS) undergoing PCI.
- Participants were randomized to potent P2Y12 inhibitor monotherapy initiated within 4 days of hospitalization versus standard 12-month DAPT with aspirin and a potent P2Y12 inhibitor.
- Assessed co-primary endpoints: a composite ischemic outcome (all-cause death, MI, stroke, and urgent target vessel revascularization) and bleeding (BARC types 2, 3, or 5).
- In STEMI, monotherapy increased 1-year ischemic composite events compared to DAPT (8.2% vs 5.2%; HR: 1.60; 95% CI: 1.14-2.24), whereas in NSTE-ACS, event rates were 5.1% vs 6.0% (HR: 0.84; 95% CI: 0.53-1.35; P for interaction = 0.030).
- Co-primary bleeding rates were lower with monotherapy than DAPT in both STEMI (HR: 0.37; 95% CI: 0.22-0.61) and NSTE-ACS cohorts (HR: 0.45; 95% CI: 0.23-0.86; P for interaction = 0.650).
Study Design
Type
RCT (n=3,410)
Structured PICO
Does potent P2Y12 inhibitor monotherapy reduce ischemic and bleeding events compared to DAPT in patients with ACS treated with PCI?
P
Population
3,410 patients with acute coronary syndrome (STEMI or NSTE-ACS) treated with percutaneous coronary intervention, followed for 12 months.
I
Intervention
Potent P2Y12 inhibitor monotherapy initiated within 4 days of hospitalization for 12 months
C
Comparator
Standard dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months
O
Outcome
Co-primary outcomes at 1 year: 1) composite of all-cause death, myocardial infarction, stroke, and urgent target vessel revascularization (ischemic outcome); and 2) Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding (bleeding outcome)composite
Main Result
Hazard Ratio: 1.6 (95% CI 1.14–2.24)
Absolute Event Rate: 8.2% vs 5.2%
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We failed to demonstrate the noninferiority of aspirin-free monotherapy initiated immediately after PCI with regard to the ischemic primary endpoint over 12 months. Results from the landmark analysis suggest that the excess ischemic 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.”
Implication
Early aspirin withdrawal and potent P2Y12 inhibitor monotherapy after PCI reduces bleeding across ACS types but increases ischemic risk specifically in STEMI patients.
Abstract
BACKGROUND The effects of very early aspirin withdrawal with potent P2Y12 inhibitor monotherapy after percutaneous coronary intervention may differ based on acute coronary syndrome (ACS) presentation. OBJECTIVES This prespecified analysis from the NEO-MINDSET trial evaluated whether treatment effects of early aspirin discontinuation differ between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS; defined as unstable angina or non-ST-segment elevation myocardial infarction). METHODS NEO-MINDSET randomized ACS patients to potent P2Y12 inhibitor monotherapy initiated within 4 days of hospitalization vs standard dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months. Co-primary outcomes were: 1) the composite of all-cause death, myocardial infarction, stroke, and urgent target vessel revascularization (ischemic outcome); and 2) Bleeding Academic Research Consortium types 2, 3, or 5 bleeding (bleeding outcome). RESULTS Of the 3,410 participants included, 2,119 (62.1%) presented with STEMI and 1,291 (37.9%) with NSTE-ACS. Among STEMI patients, an early aspirin-free strategy was associated with a higher rate of the co-primary ischemic composite outcome compared with DAPT at 1 year (8.2% vs 5.2%, respectively; HR: 1.60; 95% CI: 1.14-2.24), whereas among those with NSTE-ACS, ischemic event rates were similar between monotherapy and DAPT (5.1% vs 6.0%, respectively; HR: 0.84; 95% CI: 0.53-1.35; P for interaction = 0.030). The co-primary bleeding outcome was lower with monotherapy than with DAPT in both STEMI (HR: 0.37; 95% CI: 0.22-0.61) and NSTE-ACS (HR: 0.45; 95% CI: 0.23-0.86) populations (P for interaction = 0.650). CONCLUSIONS In patients with STEMI treated with percutaneous coronary intervention, early aspirin withdrawal may be harmful, because it increases the risk of ischemic events. Conversely, in NSTE-ACS, potent P2Y12 inhibitor monotherapy may be a viable therapeutic option: Ischemic event rates were similar and bleeding was reduced compared with DAPT. (Percutaneous Coronary Intervention Followed by Antiplatelet Monotherapy in the Setting of Acute Coronary Syndromes [NEOMINDSET]; NCT04360720).
Discussion
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Cite This Study
Tavares et al. (2025) conducted an RCT in Acute coronary syndrome (ACS) (n=3,410). Potent P2Y12 inhibitor monotherapy vs. Standard dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor was evaluated on Composite of all-cause death, myocardial infarction, stroke, and urgent target vessel revascularization (ischemic outcome) in STEMI patients (HR 1.60, 95% CI 1.14-2.24). Early potent P2Y12 inhibitor monotherapy increased ischemic events vs DAPT in STEMI patients (HR 1.60; 95% CI 1.14-2.24) but not in NSTE-ACS, while reducing bleeding in both groups.