The PREMIUM trial found low-dose prasugrel monotherapy initiated before primary percutaneous coronary intervention (PCI) was not noninferior to 12 months of dual antiplatelet therapy (DAPT) for death, stroke, or myocardial infarction in patients with ST-segment elevation myocardial infarction (STEMI)1.
Current European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association guidelines recommend DAPT with a potent P2Y12 inhibitor and aspirin for up to 12 months following PCI in STEMI, though abbreviated DAPT regimens of 1 to 3 months followed by P2Y12 monotherapy have shown reduced bleeding without a substantial ischemic penalty in prior trials. PREMIUM investigators sought to test omission of aspirin entirely from the start, rather than after an initial DAPT run-in period, using contemporary imaging-guided PCI with newer-generation drug-eluting stents.
“Previous randomised trials have demonstrated the safety of 1-3 months of DAPT followed by P2Y12 inhibitor monotherapy compared with 12 months of DAPT,” said Gaku Nakazawa, MD, PhD, principal investigator, Department of Cardiology, Kindai University Faculty of Medicine. “However, the safety of initiating prasugrel as monotherapy at the time of contemporary imaging-guided PCI compared with standard 12-month DAPT remains unknown.”2
PREMIUM trial design and primary outcome results
PREMIUM was an investigator-initiated, multicenter, open-label, noninferiority trial conducted at 69 centers in Japan from April 2023 through December 2024. Patients with STEMI undergoing primary PCI with a platinum-chromium everolimus-eluting stent (Synergy, Boston Scientific) were randomized 1:1, before PCI, to low-dose prasugrel monotherapy (20-mg loading dose, 3.75-mg daily maintenance, without aspirin) or DAPT with aspirin (162- to 200-mg loading, 81- to 100-mg daily) plus prasugrel for 12 months. The full analysis population included 1109 patients in the monotherapy group and 1107 in the DAPT group, with a prespecified noninferiority margin of 1.50 for the hazard ratio.
At 12 months, the primary composite outcome of death from any cause, stroke, or myocardial infarction occurred in 124 patients (Kaplan-Meier estimate, 11.0%) in the monotherapy group versus 94 patients (8.5%) in the DAPT group (hazard ratio [HR], 1.34; 95% CI, 1.02-1.75; P = .40 for noninferiority)1. Because the upper boundary of the confidence interval exceeded the 1.50 margin, noninferiority was not established.
Bleeding outcomes and safety profile with prasugrel monotherapy
Because noninferiority was not shown for the primary outcome, formal superiority testing of the major secondary bleeding outcome was not performed per the prespecified sequential testing strategy.
Major bleeding, defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 events, occurred in 61 patients (5.6%) in the monotherapy group compared with 92 patients (8.4%) in the DAPT group (HR, 0.66; 95% CI, 0.47-0.91) at 12 months1. Myocardial infarction alone was more frequent with monotherapy (2.9% vs 1.3%; HR, 2.24; 95% CI, 1.19-4.21), while definite or probable stent thrombosis rates were similar between groups (1.4% vs 1.5%; HR, 0.94; 95% CI, 0.46-1.89). Serious adverse events occurred in 17.2% of the monotherapy group and 16.5% of the DAPT group, and gastrointestinal bleeding accounted for a substantial share of major bleeding events in the DAPT group despite proton-pump inhibitor use in roughly 90% of those patients.
“These findings do not support prasugrel monotherapy at the time of primary PCI for STEMI,” said Nakazawa. “It appears DAPT is needed for at least the first month but the optimum duration of DAPT remains to be determined.”2
Investigators noted the increased ischemic risk with early aspirin omission mirrored findings from the NEO-MINDSET trial, despite differing randomization timing, suggesting the signal is not explained solely by prasugrel dosing or regional practice. The trial authors concluded further studies are needed to define the optimal antiplatelet regimen following STEMI, and results were presented in a Hot Line session at ESC Congress 2026 in Munich.
References
Takahashi K, Kozuma K, Morino Y, et al. Aspirin omission at the time of primary percutaneous coronary intervention in STEMI. N Engl J Med. Published August 29, 2026. doi:10.1056/NEJMoa2606997
European Society of Cardiology. Is aspirin needed after a STEMI heart attack? Published August 29, 2026. Accessed August 29, 2026.
