Leaving aspirin out of the drugs given to patients having a major heart attack led to more deaths, repeat heart attacks and strokes over the next year, according to the PREMIUM trial presented on 29 August at ESC Congress 2026 in Munich and published the same day in the New England Journal of Medicine. Among the 2,216 patients randomized in Japan, 1,109 to the single drug and 1,107 to the standard combination, the group that skipped aspirin bled less but did worse on the outcomes that matter most.
Key takeaways
- Death, heart attack or stroke at one year hit 11.0% of patients on the single drug versus 8.5% of those on the standard two-drug combination.
- Serious bleeding moved the other way, 5.6% versus 8.4%, roughly a third less.
- The investigators concluded the results do not support dropping aspirin at the time of stenting.
What the study found
PREMIUM enrolled patients having a STEMI, the kind of heart attack where an artery is fully blocked and reopened with an emergency stent. They were randomized 1:1 to either prasugrel alone, a potent anti-clotting drug started before the procedure, or the standard combination of aspirin plus prasugrel for 12 months.
The primary endpoint, death from any cause plus heart attack plus stroke at 12 months, occurred in 11.0% of the aspirin-free group and 8.5% of the combination group. That is a 2.5 percentage point gap, about 25 more such events per 1,000 patients in a year, and about 34% higher risk in relative terms (hazard ratio 1.34), very likely between 2% and 75% higher (95% CI 1.02 to 1.75). The trial was built to test whether going without aspirin was no worse, and it fell well short of that bar (p=0.40 for noninferiority).
Serious bleeding ran the opposite way. Major bleeding occurred in 5.6% of the aspirin-free group and 8.4% of the combination group, about 28 fewer serious bleeds per 1,000 patients, or roughly 34% lower risk (hazard ratio 0.66). Because the main test was not met, the ESC noted this bleeding comparison was not analyzed statistically.
Stent-related problems, including stent thrombosis, were similar in both groups.
“These findings do not support prasugrel monotherapy at the time of primary PCI for STEMI,” said principal investigator Dr. Gaku Nakazawa of Kindai University in Osaka, Japan. “It appears that DAPT is needed for at least the first month but the optimum duration of DAPT remains to be determined.”
Dr. Kumar’s take
The public has spent years absorbing the message that daily aspirin is not worth it. That message is aimed at healthy people with no known heart disease, and for that group it is reasonable. This trial is the clean counterexample showing the two situations are not the same. After an emergency stent, aspirin is still buying a lower risk of dying or having a stroke, and the price is more bleeding.
The tradeoff is about 25 extra deaths, heart attacks and strokes per 1,000 against about 28 fewer serious bleeds per 1,000. Those look close to even until you weigh each column. A gastrointestinal bleed is usually survivable and treatable. A stroke often is not reversible.
A trial that fails is more useful here than one that succeeds. Cutting back on antiplatelet therapy has had momentum for years, driven by earlier trials that shortened the two-drug window to one to three months. Going all the way to zero aspirin from day one was the obvious next step, and someone had to test it rather than assume it. Heart disease is a condition where nearly 9 in 10 US deaths are preventable, and that holds only if existing treatments keep working.
Three limits belong on the record. The trial was open-label, so everyone knew who was taking what. It ran entirely in Japan using low-dose prasugrel, so the results do not transfer cleanly. And it was funded by Boston Scientific.
What it means for you
If you have had a stent placed for a heart attack, do not stop aspirin on your own. Stopping an antiplatelet drug early is one of the few decisions in cardiology where the downside arrives fast. Take the question to the cardiologist who placed the stent, because the length of the two-drug window is a judgment call that depends on your bleeding risk.
If you have never had a heart attack, a stent or a stroke, this trial says nothing about you. The debate over daily aspirin in healthy adults is a separate one, and this result does not reopen it.
If bleeding on two drugs has been a problem for you, raise it rather than sit on it. The bleeding difference here was real, and shortening the window is a recognized option some patients qualify for, but that is a conversation to have with a cardiologist, not a change to make at the kitchen table.