Prasugrel monotherapy versus 12-month dual antiplatelet therapy in STEMI patients undergoing intravascular imaging-guided PCI: Study design and rationale of the randomized PREMIUM trial.

BACKGROUND: Previous randomized trials have demonstrated the safety of P2Y12 inhibitor monotherapy after 1-3 months of dual antiplatelet therapy (DAPT) compared with 12-month DAPT following percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. However, the safety of initiating prasugrel monotherapy at the time of primary PCI in patients presenting with ST-segment elevation myocardial infarction (STEMI) remains unknown.

METHODS/DESIGN: The PREMIUM (Prasugrel monotherapy following primary percutaneous coronary intervention for ST-elevation myocardial infarction) trial is an investigator-initiated, open-label, multicenter randomized controlled trial. A total of 2268 STEMI patients indicated for primary PCI with current generation platinum‑chromium everolimus-eluting stents were randomized 1:1 to either prasugrel monotherapy (20 mg loading, 3.75 mg daily) initiated before PCI or standard 12-month DAPT with aspirin plus prasugrel. The primary endpoint is a composite of all-cause death, myocardial infarction, or stroke at 12 months tested for noninferiority. The major secondary endpoint is Bleeding Academic Research Consortium type 3 or 5 bleeding at 12 months tested for superiority.

SUMMARY: The PREMIUM trial is the first large-scale randomized study to evaluate an upfront aspirin-free strategy with prasugrel monotherapy compared with standard 12-month DAPT in STEMI undergoing contemporary imaging-guided PCI. The trial is designed to determine noninferiority for ischemic outcomes and to assess superiority in reducing major bleeding at 12 months in East Asian patients.

TRIAL REGISTRATION: NCT05709626; jRCTs052220145.