PREMIUMAcute Coronary SyndromesNew England Journal of Medicine
Prasugrel Monotherapy Versus Dual Antiplatelet Therapy in Primary Percutaneous Coronary...
Aspirin Omission at the Time of Primary Percutaneous Coronary Intervention in STEMI
View Full PaperWhy the trial?
Aspirin is standard at primary PCI, yet it adds bleeding risk on top of potent P2Y12 inhibition. PREMIUM asked whether omitting aspirin at the time of primary PCI for ST-elevation myocardial infarction preserves ischaemic protection while reducing bleeding.
Does low-dose prasugrel monotherapy prevent death, stroke, or myocardial infarction in patients with STEMI undergoing primary PCI compared to DAPT with aspirin and low-dose prasugrel?
Population
2216 STEMI patients undergoing primary PCI in Japan
Comparison
Low-dose prasugrel monotherapy (aspirin omitted) vs DAPT with aspirin + prasugrel
Design
Multicenter open-label randomized noninferiority trial (HR margin 1.50)
Follow-up
12 months
Key result
Low-dose prasugrel monotherapy was not noninferior to DAPT for the composite of death, stroke, or MI at 12 months (HR 1.34; 95% CI 1.02-1.75; P=0.40 for noninferiority).
Authors
Discussion
Key questions
Member takes
Where experts stand
Experts read PREMIUM as a clear negative: omitting aspirin upfront in STEMI is not safe, and the consensus is that aspirin still belongs at the time of primary PCI.
The reaction to PREMIUM is overwhelmingly one-sided. Clinicians agree that skipping aspirin from the start in STEMI carries an ischemic cost that reduced bleeding does not offset. The live question is whether these results apply broadly or reflect features specific to the Japanese population and low-dose prasugrel used in this trial, and how the finding fits alongside other recent aspirin-omission trials that tested de-escalation at later time points.
Agreement
Multiple clinicians converge on the same point: aspirin should not be omitted at the time of primary PCI in STEMI. Several note that the bleeding reduction seen with monotherapy does not compensate for the higher ischemic event rate.
4 clinicians say this directly
What they’re arguing about
supportiveneutralcautiouscritical
Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.
Still unclear
Whether PREMIUM's findings generalize beyond East Asian patients on low-dose prasugrel remains an open question. Several experts note that the timing of aspirin omission matters, pointing to trials like TARGET-FIRST where later de-escalation after an uneventful DAPT period showed different results. How guidelines should now frame the role of early versus delayed aspirin withdrawal after ACS is unresolved.
Key expert perspectives
Aspirin's demise is overstated: timing and patient phenotype matter
Argues that both NEOMINDSET and PREMIUM show early aspirin omission is harmful in STEMI, while TARGET-FIRST's benefit applied only to low-risk patients one month after uneventful DAPT. Aspirin omission is not one-size-fits-all, and the distinction between upfront omission and later de-escalation is critical.
The chatter for P2Y12 inhibitor monotherapy in ACS should finally subside
Declares that with NEOMINDSET, TARGET FIRST, and now PREMIUM, the case for dropping aspirin in ACS is weakened, and guidelines should take note.
Distilled from their postX post
Aspirin should be given upfront, with de-escalation considered later
Frames PREMIUM as testing what happens when aspirin is never given at all, concluding that prasugrel monotherapy started before the procedure was not noninferior. Recommends upfront aspirin followed by later de-escalation.
Overview
Prasugrel monotherapy is not noninferior to DAPT after STEMI PCI; challenges early aspirin omission and reinforces dual therapy for ischemic protection.
Key Points
- To determine whether omitting aspirin and using low-dose prasugrel monotherapy is noninferior to dual antiplatelet therapy (DAPT) in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).
- Multicenter, open-label randomized trial (PREMIUM, NCT05709626) in Japan randomly assigning 2216 patients with STEMI (1:1) before primary PCI to 12 months of low-dose prasugrel monotherapy (N=1109) or DAPT with aspirin plus low-dose prasugrel (N=1107).
- The primary outcome was a composite of death from any cause, stroke, or myocardial infarction at 12 months, assessed with a prespecified noninferiority hazard ratio margin of 1.50.
- The primary composite outcome occurred in 11.0% (124 patients) in the monotherapy group versus 8.5% (94 patients) in the DAPT group (HR 1.34; 95% CI, 1.02 to 1.75; P=0.40 for noninferiority), failing to meet the noninferiority margin.
- Major bleeding (BARC type 3 or 5) occurred in 5.6% (61 patients) in the monotherapy group versus 8.4% (92 patients) in the DAPT group (HR 0.66; 95% CI, 0.47 to 0.91).
Evidence details
What drove the result?
| Outcome | Prasugrel mono | DAPT |
|---|---|---|
| Death, stroke, or MI at 12 months | 124 (11.0%) | 94 (8.5%) |
| HR 1.34 (95% CI 1.02-1.75); P=0.40 - noninferiority NOT met; CI compatible with harm | ||
Limitations & tradeoffs
Safety
Major bleeding (BARC 3 or 5) 61 (5.6%) vs 92 (8.4%); HR 0.66 (95% CI 0.47-0.91) — lower with monotherapy, opposite direction from ischemic events.
Statistical certainty
the primary hazard ratio's CI (1.02-1.75) excludes 1, indicating possible ischemic harm from aspirin omission.
Representation
conducted only in Japan with low-dose prasugrel, which may limit generalizability to other dosing practices.
Design limitations
open-label design.
Structured PICO
Does low-dose prasugrel monotherapy prevent death, stroke, or myocardial infarction in patients with STEMI undergoing primary PCI compared to DAPT with aspirin and low-dose prasugrel?
P
Population
2,216 patients with STEMI undergoing primary PCI, followed for 12 months.
I
Intervention
Low-dose prasugrel monotherapy initiated before PCI for 12 months.
C
Comparator
Dual antiplatelet therapy (DAPT) with aspirin and low-dose prasugrel for 12 months.
O
Outcome
Composite of death from any cause, stroke, or myocardial infarction at 12 months.composite
In patients with STEMI undergoing primary PCI, omitting aspirin and using low-dose prasugrel monotherapy was not noninferior to standard DAPT for ischemic outcomes at 12 months, despite reducing major bleeding.
Main Result
Hazard Ratio: 1.34 (95% CI 1.02–1.75)
Absolute Event Rate: 11% vs 8.5%
p-value: p=0.40 for noninferiority
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Takahashi et al. (2026) conducted an RCT in ST-segment elevation myocardial infarction (STEMI) (n=2,216). Low-dose prasugrel monotherapy vs. Dual antiplatelet therapy (DAPT) with aspirin and low-dose prasugrel was evaluated on Composite of death from any cause, stroke, or myocardial infarction at 12 months (HR 1.34, 95% CI 1.02-1.75, p=0.40 for noninferiority). Low-dose prasugrel monotherapy was not noninferior to DAPT for the composite of death, stroke, or MI at 12 months (HR 1.34; 95% CI 1.02-1.75; P=0.40 for noninferiority).