Trial Finds Prasugrel Alone Falls Short of Standard Care After Heart Attack

A large Japanese trial has found that using the antiplatelet drug prasugrel alone, without aspirin, at the time of emergency heart-attack treatment does not work as well as standard dual therapy. The PREMIUM trial, presented in a Hot Line session at the European Society of Cardiology (ESC) Congress 2026 and published simultaneously in the New England Journal of Medicine, tested prasugrel monotherapy against standard dual antiplatelet therapy (DAPT) -- a potent P2Y12 inhibitor plus aspirin -- in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), a severe type of heart attack.

ESC guidelines generally recommend 12 months of DAPT after PCI, though the duration can be shortened in some cases. "The safety of initiating prasugrel as monotherapy at the time of contemporary imaging-guided PCI compared with standard 12-month DAPT remains unknown," said principal investigator Dr. Gaku Nakazawa of Kindai University in Osaka, Japan, explaining why the open-label trial was carried out at 69 centres in Japan.

The trial randomly assigned 2,280 patients, whose average age was about 69 and 23% of whom were women, to receive either prasugrel monotherapy or standard DAPT for 12 months. The primary endpoint -- death, heart attack or stroke within 12 months -- occurred in 11.0% of the prasugrel-monotherapy group compared with 8.5% of the DAPT group, meaning the trial did not demonstrate noninferiority. Significant bleeding was less common with monotherapy, occurring in 5.6% of patients versus 8.4% on DAPT, though stent-related complications were similar between the two groups and non-stent-related events were more frequent with monotherapy.

"These findings do not support prasugrel monotherapy at the time of primary PCI for STEMI," Nakazawa concluded. "It appears that DAPT is needed for at least the first month, but the optimal duration of DAPT remains to be determined."