Noninferiority was not demonstrated for death and ischemic events between P2Y12 inhibitor monotherapy and dual antiplatelet therapy (DAPT) given for 12 months after stenting in patients with acute coronary syndromes (ACS), according to late-breaking research presented in a Hot Line session at the ESC Congress 2025 and simultaneously published in the New England Journal of Medicine.

DAPT consisting of aspirin plus a potent P2Y12 inhibitor for 12 months is recommended for patients with ACS (myocardial infarction [MI] and unstable angina) after percutaneous coronary intervention (PCI) with stent implantation.

“Recent evidence suggests that withdrawal of aspirin after one to three months of DAPT, followed by P2Y12 inhibitor monotherapy may reduce bleeding while preventing recurrent ischemic events compared with 12 months of DAPT,” noted Principal Investigator, Professor Pedro Lemos from the Hospital Israelita Albert Einstein, Sao Paulo, Brazil.

“We conducted the NEO-MINDSET trial to specifically investigate if P2Y12 inhibitor monotherapy could be used in the early phase, immediately after PCI and for the entire 12 months compared with DAPT for 12 months.”

The open-label randomized controlled NEO-MINDSET trial was conducted across 50 sites in Brazil. Patients with ACS undergoing successful PCI with drug-eluting stents were randomized 1:1 within the first four days of hospitalization to stop aspirin and receive potent P2Y12 inhibitor monotherapy (ticagrelor or prasugrel) or to DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months.

The first primary outcome was a composite of death, MI, stroke or urgent target-vessel coronary revascularization, with an absolute risk difference of 2.5 percentage points set as the prespecified noninferiority margin. The second primary outcome was major or clinically relevant nonmajor bleeding, with superiority testing if the first primary outcome was noninferior.

The analysis population included 3,410 randomized patients who had a mean age of 59.6 years, with 29.3% being women.

The ischemic primary endpoint occurred in 7.0% of patients in the monotherapy group and 5.5% in the DAPT group (hazard ratio [HR] 1.28; 95% confidence interval [CI], 0.98 to 1.68), resulting in an absolute risk difference of +1.47 percentage points (95% CI, −0.16 to 3.10), which did not meet the prespecified criteria for noninferiority (p=0.11).

Major or clinically relevant nonmajor bleeding occurred in 2.0% of patients in the monotherapy group and 4.9% in the DAPT group (risk difference −2.97 percentage points; 95% CI −4.20 to −1.73).

The incidence of all-cause death was 3.6% in the monotherapy group and 3.0% in the DAPT group (HR 1.24; 95% CI 0.85 to 1.79). Any bleeding occurred in 4.5% of patients in the monotherapy group and 9.0% in the DAPT group.

A landmark analysis on the ischemic primary endpoint revealed a risk difference of +1.5 percentage points during the first 30 days and 0.0 percentage points from 30 days to 12 months for P2Y12 inhibitor monotherapy vs. DAPT. For the bleeding primary endpoint, the risk difference was −0.8 percentage points during the first 30 days and −2.2 percentage points from 30 days to 12 months for monotherapy vs. DAPT.

Summarizing the findings, Professor Lemos concluded, “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.”