Clinical ACS presentation modulates treatment effects of very early aspirin withdrawal versus DAPT

In a NEO-MINDSET substudy among ACS patients treated with PCI, potent P2Y₁₂ inhibitor monotherapy ≤4 days after hospitalization was associated with a higher risk of ischemic events compared with dual antiplatelet therapy (DAPT) in STEMI but not non–ST elevation ACS.

This summary is based on the publication of Tavares CAM, Guimarães PO, Franken M, et al. - Potent P2Y12 Inhibitor Monotherapy vs DAPT After PCI in Patients With and Without STEMI: The NEO-MINDSET Substudy. J Am Coll Cardiol. 2026 Jan 27;87(3):297-308. doi: 10.1016/j.jacc.2025.10.058

Introduction and methods

Background

Meta-analyses of RCT data have suggested that dual antiplatelet therapy (DAPT) for 1–6 months followed by monotherapy with a potent P2Y₁₂ inhibitor reduces bleeding risk in ACS patients undergoing PCI compared with 12-month DAPT, without increasing ischemic events [1,2]. However, strong evidence for the efficacy of P2Y₁₂ inhibitor monotherapy initiated in the first month after an ACS event is lacking. In addition, the effects of antiplatelet strategies may differ between patients with STEMI and those with non–ST-segment elevation ACS (NSTE-ACS) due to pathophysiologic differences.

In the NEO-MINDSET (Percutaneous Coronary Intervention Followed by Antiplatelet Monotherapy in the Setting of Acute Coronary Syndromes) trial, potent P2Y₁₂ inhibitor monotherapy initiated shortly after successful PCI was not found to be noninferior to DAPT in reducing a composite outcome of ischemic events or death at 12 months among all ACS patients [3].

Aim of the study

In a prespecified analysis of the NEO-MINDSET trial, the effect of very early aspirin discontinuation compared with DAPT was evaluated in ACS patients treated with PCI, stratified by clinical presentation (STEMI vs. NSTE-ACS).

Methods

The NEO-MINDSET trial was a multicenter, open-label, phase 3 RCT conduced in Brazil in which 3410 ACS patients were randomized to either monotherapy with a potent P2Y₁₂ inhibitor (ticagrelor 90 mg twice daily or prasugrel 5–10 mg daily, based on clinical preference) initiated ≤4 days after hospitalization or standard DAPT with aspirin and a potent P2Y₁₂ inhibitor for 12 months [4]. NSTE-ACS was defined as unstable angina or NSTEMI. Of the study participants, 2119 (62.1%) presented with STEMI and 1291 (37.9%) with NSTE-ACS.

Outcomes

The coprimary endpoints were: (1) a composite ischemic outcome of all-cause mortality, MI, stroke, or urgent target vessel revascularization at 12 months; and (2) major or clinically relevant nonmajor bleeding events, defined as Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events, at 12 months.

Secondary endpoints included the individual components of the coprimary endpoints, CV death, stent thrombosis, and net adverse clinical events (i.e., a combination of the individual components of the coprimary ischemic and bleeding endpoints). All endpoints were adjudicated by an independent clinical events committee.

Main results

Ischemic outcome

• Among STEMI patients, the cumulative incidence of the coprimary ischemic outcome was 8.2% in participants receiving monotherapy (n=1058) and 5.2% in those on DAPT (n=1061) (HR: 1.60; 95%CI: 1.14–2.24).
• In contrast, in the group of NSTE-ACS patients, the 12-month ischemic event rate was similar in the monotherapy (n=654) and DAPT (n=637) arms (5.1% vs. 6.0%; HR: 0.84; 95%CI: 0.53–1.35; P for interaction=0.030).
• Significant interactions were also observed for the incidence rates of MI (P for interaction=0.005) and net adverse clinical events (P for interaction=0.040).

Bleeding outcome

• In the group of STEMI patients, the coprimary bleeding outcome occurred in 1.9% of the participants in the monotherapy arm and 5.2% of those on DAPT (HR: 0.37; 95%CI: 0.22–0.61).
• A similar treatment effect was seen in NSTE-ACS patients (2.0% vs. 4.5%; HR: 0.45; 95%CI: 0.23–0.86; P for interaction=0.650).
• There were 3 fatal bleeding events (BARC type 5): 2 among STEMI patients who received DAPT and 1 in an NSTE-ACS patient receiving monotherapy.

Conclusion

In this NEO-MINDSET substudy among ACS patients treated with PCI, the clinical presentation modulated the treatment effects of very early potent P2Y₁₂ inhibitor monotherapy (i.e., ≤4 days after hospitalization) versus DAPT. In patients with STEMI, monotherapy was associated with a higher risk of the composite ischemic outcome (all-cause mortality, MI, stroke, or urgent target vessel revascularization) at 12 months compared with DAPT, whereas there was no difference in ischemic risk among those with NSTE-ACS. Both STEMI and NSTE-ACS patients showed lower bleeding rates with monotherapy compared with DAPT. The authors conclude that “in NSTE-ACS, potent P2Y₁₂ inhibitor monotherapy may be a viable therapeutic option.”

Find this article online at J Am Coll Cardiol.

References

1. Galli M, Laudani C, Occhipinti G, et al. P2Y12 inhibitor monotherapy after short DAPT in acute coronary syndrome: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2024;10:588–598.
2. Carvalho PEP, Gewehr DM, Nascimento BR, et al. Short-term dual antiplatelet therapy after drug-eluting stenting in patients with acute coronary syndromes: a systematic review and network meta-analysis. JAMA Cardiol. 2024;9: 1094–1105.
3. Guimaraes PO, Franken M, Tavares CAM, et al. Early withdrawal of aspirin after PCI in acute coronary syndromes. N Engl J Med. 2025;393(21): 2095–2106.
4. Guimaraes PO, Franken M, Tavares CAM, et al. P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEO-MINDSET Trial. EuroIntervention. 2023;19: e323–e329.