Design: Multicentre, open-label, randomised non-inferiority trial
Population: 2,216 patients with STEMI undergoing primary PCI in Japan
Primary outcome: Death, stroke or MI at 12 months
Effect: 11.0% vs 8.5%; HR 1.34 (95% CI 1.02–1.75), non-inferiority not met

PREMIUM randomised 2,216 Japanese patients with STEMI, before primary PCI, to low-dose prasugrel alone or low-dose prasugrel plus aspirin for 12 months. The aim was to show that dropping aspirin from the start was safe.

It was not. Death, stroke or MI at 12 months occurred in 11.0% on monotherapy and 8.5% on dual therapy (HR 1.34, 95% CI 1.02–1.75), failing the non-inferiority margin of 1.50. Major bleeding was lower without aspirin (5.6% vs 8.4%, HR 0.66, 0.47–0.91), and stent thrombosis appeared similar.

Aspirin-free strategies have looked promising in stable and later-phase settings, but the acute STEMI window is where thrombotic risk is highest. This trial suggests that trading ischaemic protection for less bleeding at the index procedure is not a good exchange. Note the prasugrel dose was the low Japanese dose, so results may not transfer exactly to standard-dose regimens.

Give aspirin loading at STEMI presentation with a P2Y12 inhibitor; do not omit it at primary PCI.
Consider shortening aspirin later in patients at high bleeding risk, but not from day one.
Expect about 3 fewer major bleeds but 2–3 more ischaemic events per 100 patients if aspirin is omitted up front.
The trial used low-dose prasugrel (Japanese dosing); interpret carefully for standard-dose ticagrelor or prasugrel.
Document the planned DAPT duration at discharge so de-escalation is a deliberate later decision.

Why it matters

It sets a limit on aspirin-free strategies: they do not extend to the acute STEMI window.

The statistics, in plain English

Non-inferiority asks whether a new approach is 'not unacceptably worse'. The upper limit of the confidence interval (1.75) exceeded the pre-set margin (1.50), so non-inferiority failed. The point estimate (1.34) and a lower limit above 1.0 actually point towards more events without aspirin. The bleeding benefit was not formally tested for superiority because the primary test failed.