Low-dose prasugrel monotherapy failed to show non-inferiority when compared to 12 months of dual antiplatelet therapy (DAPT) against a composite endpoint of all-cause death, stroke or myocardial infarction (MI) in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI).
This was the major finding of the PREMIUM trial, an investigator-initiated, open-label, noninferiority trial conducted at 69 centres in Japan among STEMI patients indicated for primary PCI with current generation platinum‑chromium everolimus-eluting stents.
Results of the trial were presented at the European Society of Cardiology’s 2026 congress (28–31 August, Munich, Germany) and published simultaneously in the New England Journal of Medicine (NEJM).
“Previous randomised trials have demonstrated the safety of one to three months of DAPT followed by P2Y12 inhibitor monotherapy compared with 12 months of DAPT. However, the safety of initiating prasugrel as monotherapy at the time of contemporary imaging-guided PCI compared with standard 12-month DAPT remains unknown,” the trial’s principal investigator, Gaku Nakazawa (Kindai University, Osaka, Japan), commented.
Eligible patients were randomised (1:1) to either prasugrel monotherapy (20 mg loading, 3.75 mg daily) initiated before PCI or standard DAPT with aspirin plus prasugrel for 12 months. Patients at high bleeding risk in the DAPT group could receive DAPT for 3 months then prasugrel monotherapy at the clinician’s discretion. A total of 2,280 patients were randomised, with a mean age of around 69 years and 23% were women.
Non-inferiority was not demonstrated for prasugrel monotherapy compared with DAPT for the primary endpoint of all-cause death, MI or stroke at 12 months. The primary endpoint occurred in 11% of patients receiving prasugrel monotherapy and in 8.5% of patients in the DAPT group (hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.02 to 1.75; p=0.40 for non-inferiority).
As noninferiority was not met, the major secondary endpoint related to bleeding was not analysed statistically. Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in 5.6% of patients in the prasugrel monotherapy group and 8.4% of patients in the DAPT group at 12 months (HR 0.66; 95% CI 0.47 to 0.91).
Definite or probable stent thrombosis and clinically driven target lesion revascularisation were similar between groups, but non-stent related events including non-target lesion revascularisation were more frequent with prasugrel monotherapy.
“These findings do not support prasugrel monotherapy at the time of primary PCI for STEMI,” concluded Nakazawa. “It appears that DAPT is needed for at least the first month but the optimum duration of DAPT remains to be determined.”
