Aspirin's demise is exaggerated and guidelines should take note
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Aspirin Omission at the Time of Primary Percutaneous Coronary Intervention in STEMI
Gaku NakazawaKuniaki TakahashiKen KozumaYoshihiro MorinoKosuke KashiwabaraHiromasa OtakeSatoru SuwaMamoru NanasatoTakashi MuramatsuHitoshi AnzaiAkihiro ShirakabeMasashi YamamotoYasuhide AsaumiMasashi SakumaHideki OkayamaKeisuke NakabayashiNobuhiko OgataKentaro JujoKohei WakabayashiTakanori KusuyamaY OnishiKazuhiro AshidaYuya MitsuhashiYuji NishimotoSeiji YamazakiNehiro KuriyamaYuji Ikari
What happened
Prasugrel monotherapy was not noninferior to 12-month DAPT for death, MI, or stroke at 12 months (11.0% vs 8.5%; HR 1.34, 95% CI 1.02–1.75; p=0.40 for noninferiority).
- 124 (11.0%) vs 94 (8.5%) at 12 months
Does this change practice?
Where experts agree
Multiple clinicians converge on the same conclusion: aspirin should not be omitted at the time of primary PCI, and these results confirm aspirin still matters in the acute STEMI setting.
What this trial adds
Experts read PREMIUM as a clear negative for aspirin-free P2Y12 inhibitor monotherapy from the start of primary PCI in STEMI, reinforcing that aspirin still matters up front.
Published field read
The reaction is nearly unanimous: dropping aspirin entirely at the time of primary PCI carries an ischemic cost that is not offset by less bleeding. Several clinicians place PREMIUM alongside other recent trials to argue that early aspirin omission in acute coronary syndromes is harmful, though later de-escalation may still be reasonable. The live question is whether these results will prompt guidelines to formally reaffirm upfront aspirin and clarify the earliest safe point for de-escalation.
Still open
Questions raised in published commentaryWhether upfront aspirin can safely be dropped in lower-risk PCI populations or at a later time point remains open, as several experts note that timing and patient phenotype may be the key variables.
Whether guidelines will now formally distinguish upfront aspirin omission from later de-escalation is unresolved.
Context from published commentary. Source summaries are not a new guideline recommendation.
Who says what
Aspirin should be given up front and de-escalation considered later
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Timing and phenotype matter: upfront aspirin omission is harmful in STEMI
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Aspirin omission fails even with intracoronary imaging and low BMI
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Aspirin-free therapy from the time of primary PCI was not benign
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Heerajnarain BulluckContextInterventional / Structural Cardiology · Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust
PREMIUM tested whether a potent P2Y12 inhibitor alone is enough from the moment the stent goes in
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2,216 patients randomised before PCI show aspirin omission did not meet noninferiority
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Ahmed BennisResults readoutHeart Failure / Cardiomyopathy · Centre Hospitalier Universitaire Hassan II
Summarizes the primary outcome: monotherapy did not meet noninferiority versus DAPT with HR 1.34.
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Notes that avoiding aspirin with prasugrel monotherapy in STEMI did not meet the noninferiority criterion.
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Reports that prasugrel monotherapy initiated before PCI was not noninferior to DAPT for death, stroke, or MI at 12 months.
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Flagged PREMIUM pre-result as a potentially practice-changing trial asking whether aspirin is still needed.
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Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Full evidence
Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Why 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?
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
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
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.
Discussion
No takes yet. Share an insight, caveat, or question.
Expert reaction
What experts said about PREMIUM
NEJM · ESC Congress 2026
Expert labels are toward PREMIUM's result, from named public quotes (n=0). As of Aug 29, 2026.
Where experts stand
Experts read PREMIUM as a clear negative for aspirin-free P2Y12 inhibitor monotherapy from the start of primary PCI in STEMI, reinforcing that aspirin still matters up front.
The reaction is nearly unanimous: dropping aspirin entirely at the time of primary PCI carries an ischemic cost that is not offset by less bleeding. Several clinicians place PREMIUM alongside other recent trials to argue that early aspirin omission in acute coronary syndromes is harmful, though later de-escalation may still be reasonable. The live question is whether these results will prompt guidelines to formally reaffirm upfront aspirin and clarify the earliest safe point for de-escalation.
Agreement
Multiple clinicians converge on the same conclusion: aspirin should not be omitted at the time of primary PCI, and these results confirm aspirin still matters in the acute STEMI setting.
5 clinicians say this directly
2 takes classified by contention axis so far — the map appears as more land.
Still unclear
Whether upfront aspirin can safely be dropped in lower-risk PCI populations or at a later time point remains open, as several experts note that timing and patient phenotype may be the key variables. Whether guidelines will now formally distinguish upfront aspirin omission from later de-escalation is unresolved.
Key expert perspectives
NNEJM
“Presented at #ESCCongress: Among patients with STEMI, prasugrel monotherapy initiated before PCI was not noninferior to dual antiplatelet therapy with prasugrel plus aspirin for a composite of death, stroke, or myocardial infarction at 12 months. Full PREMIUM trial results:”
Aspirin's demise is exaggerated and guidelines should take note
Argues that PREMIUM, together with NEOMINDSET and TARGET FIRST, should end the push for P2Y12 inhibitor monotherapy in ACS. Calls on guidelines to reflect this.
Distilled from their postX post
Aspirin should be given up front and de-escalation considered later
Notes that PREMIUM asked what happens when aspirin is never given at all. Concludes that prasugrel monotherapy started before the procedure was not noninferior, and aspirin should be given up front with de-escalation considered afterward.
Implication
Prasugrel monotherapy is not noninferior to DAPT after STEMI PCI; challenges early aspirin omission and reinforces dual therapy for ischemic protection.
Abstract
BackgroundThe safety of omitting up-front treatment with aspirin during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. MethodsWe conducted a multicenter, open-label, randomized trial in Japan involving patients with STEMI who were undergoing primary PCI. Patients were randomly assigned in a 1:1 ratio before PCI to receive low-dose prasugrel monotherapy or dual antiplatelet therapy (DAPT) with aspirin and low-dose prasugrel for 12 months. The primary outcome was a composite of death from any cause, stroke, or myocardial infarction at 12 months, which was assessed for noninferiority with a prespecified noninferiority margin of 1.50 for the 95% confidence interval of the hazard ratio. The major secondary outcome was major bleeding (defined as a bleeding event of Bleeding Academic Research Consortium [BARC] type 3 [nonfatal major bleeding] or 5 [fatal bleeding]) at 12 months, which was assessed for superiority if noninferiority was established for the primary outcome. ResultsA total of 2216 patients were included in the full analysis population; 1109 were assigned to receive monotherapy and 1107 to receive DAPT. At 12 months, death from any cause, stroke, or myocardial infarction had occurred in 124 patients (Kaplan–Meier estimate, 11.0%) in the monotherapy group and in 94 patients (Kaplan–Meier estimate, 8.5%) in the DAPT group (hazard ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.75; P=0.40 for noninferiority). Major bleeding had occurred in 61 patients (Kaplan–Meier estimate, 5.6%) in the monotherapy group and in 92 patients (Kaplan–Meier estimate, 8.4%) in the DAPT group (hazard ratio, 0.66; 95% CI, 0.47 to 0.91). The percentages of patients with definite or probable stent thrombosis and serious adverse events appeared to be similar in the two groups. ConclusionsAmong patients with STEMI who were undergoing primary PCI, low-dose prasugrel monotherapy initiated before PCI was not noninferior to DAPT for 12 months with respect to a composite of death from any cause, stroke, or myocardial infarction at 12 months. (Funded by Boston Scientific Japan; PREMIUM ClinicalTrials.gov number, NCT05709626.)
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).