One-Month Outcomes of Aspirin-Free Strategy for Percutaneous Coronary Intervention With or Without Proton-Pump Inhibitors　― A Post Hoc Subgroup Analysis of STOPDAPT-3 ―

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Acute coronary syndrome or high bleeding risk undergoing percutaneous coronary intervention (n=5654). Intervention: Aspirin-free strategy (prasugrel monotherapy) vs. Dual antiplatelet therapy (aspirin 81-100 mg/day + prasugrel 3.75 mg/day). Primary outcome: Co-primary cardiovascular endpoint (composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) in the no-PPI subgroup (HR 0.13, 95% CI 0.03-0.60, p=0.01).

Q: What does this research mean for the field?

An aspirin-free strategy after percutaneous coronary intervention significantly reduces early cardiovascular events compared to dual antiplatelet therapy in patients not co-prescribed proton-pump inhibitors, while no interaction is observed for bleeding outcomes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ryota Nishio; Hirotoshi Watanabe; Takeshi Morimoto; M Natsuaki; Ko Yamamoto; Yuki Obayashi; Ryusuke Nishikawa; Tomoya Kimura; Manabu Ogita; Hideki Wada; Hirohisa Endo; Jun Shitara; K Ando; Takenori Domei; T Isawa; Hiroyuki Takenaka; Takashi Yamamoto; Tetsuya Ishikawa; Itaru Hisauchi; Hideo Tokuyama; Hiroki Sakamoto; Takanari Fujita; Mamoru Nanasato; Hideki Okayama; Satoru Suwa; Koh Ono; Takeshi Kimura; on behalf of the STOPDAPT-3 Investigators

doi:10.1253/circrep.cr-26-0156

Key result

Aspirin-free prasugrel monotherapy cuts cardiovascular events ~87% versus DAPT in patients not taking PPIs.

HR 0.13
95% CI 0.03-0.60
P=0.01
n=5,654

Figures

Why the study?

Previous reports had not explored the interaction of proton-pump inhibitors on the early effect of an aspirin-free strategy compared with DAPT after PCI.

Does an aspirin-free strategy compared to DAPT reduce bleeding or cardiovascular events in PCI patients stratified by proton-pump inhibitor (PPI) use?

Key Points

To evaluate whether proton-pump inhibitor (PPI) prescription modifies the 30-day bleeding and cardiovascular effects of an aspirin-free strategy compared with dual antiplatelet therapy (DAPT) after percutaneous coronary intervention.
Post hoc subgroup analysis of 5,654 patients discharged alive within 30 days after randomization in STOPDAPT-3.
Patients were stratified by PPI prescription at discharge (PPI subgroup: n=4,958; no-PPI subgroup: n=696) and randomized treatment (no-aspirin vs. DAPT).
Assessed co-primary bleeding (BARC 3 or 5) and cardiovascular endpoints (composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 30 days.
For the co-primary bleeding endpoint, no significant interaction occurred between PPI prescription and antiplatelet regimen (PPI: 3.23% vs. 3.57%; HR 0.90; 95% CI 0.66–1.22; no-PPI: 1.45% vs. 2.80%; HR 0.52; 95% CI 0.17–1.54; P interaction=0.34).
For the co-primary cardiovascular endpoint, a lower risk with no aspirin versus DAPT appeared in the no-PPI subgroup (0.41% vs. 3.27%; HR 0.13; 95% CI 0.03–0.60; P=0.01) but not the PPI subgroup (2.12% vs. 1.65%; HR 1.29; 95% CI 0.86–1.93; P=0.23), showing a significant interaction (P interaction=0.005).

Study Design

Type

RCT (n=5,654)

Blinding

Open-label

Randomization

1:1

Multicenter

Yes

Structured PICO

Does an aspirin-free strategy compared to DAPT reduce bleeding or cardiovascular events in PCI patients stratified by proton-pump inhibitor (PPI) use?

P

Population

5,654 patients (mean age 71.4 years, 23.2% female) with acute coronary syndrome or high bleeding risk undergoing percutaneous coronary intervention, followed for 1 month to evaluate an aspirin-free strategy stratified by proton-pump inhibitor use.

I

Intervention

Aspirin-free strategy consisting of low-dose prasugrel monotherapy (3.75 mg/day)

C

Comparator

Dual antiplatelet therapy (DAPT) consisting of aspirin (81-100 mg/day) and low-dose prasugrel (3.75 mg/day)

O

Outcome

Co-primary bleeding endpoint (Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) and co-primary cardiovascular endpoint (composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 monthcomposite

Main Result

Hazard Ratio: 0.13 (95% CI 0.03–0.6)

Absolute Event Rate: 0.41% vs 3.27%

Absolute Risk Reduction: 2.86%

p-value: p=0.01

Limitations

PPI use was left to the discretion of each attending physician and was not controlled at randomization, resulting in baseline differences.
Classification of PPI use was based on prescription at hospital discharge, not at randomization.
Post hoc, exploratory subgroup analysis not prespecified in the original protocol.
Dose of prasugrel (3.75 mg daily) was different from the international standard dose of 10 mg.
Underpowered for rare events like GI bleeding and stent thrombosis with short-term outcomes.
Included only Japanese patients, limiting generalizability.
PPI use was left to the discretion of each attending physician, resulting in baseline differences and potential selection bias.
Inter-institutional variations in prescribing patterns and clinical practices.
Underpowered for rare events like GI bleeding and stent thrombosis with short-term outcomes (30 days).

Implication

PPI use may warrant caution with aspirin-free P2Y12 monotherapy post-PCI; leaves open causal interaction versus confounding.

Abstract

Background: There are no previous reports exploring the interaction of proton-pump inhibitors (PPI) on the early effect of aspirin-free strategy compared with dual antiplatelet therapy (DAPT) after PCI. Methods and Results: Among 5,654 patients who were discharged alive within 30 days after randomization in ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3), 4,958 patients received PPI prescriptions (PPI subgroup; no-aspirin group, n=2,356; and DAPT group, n=2,602), and 696 patients did not (no-PPI subgroup; no-aspirin group, n=482; and DAPT group, n=214). The co-primary bleeding endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding, and the co-primary cardiovascular endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. No significant interaction was observed between PPI prescription and antiplatelet regimen on the bleeding endpoint (PPI: hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.66–1.22; no-PPI: HR 0.52; 95% CI 0.17–1.54; P interaction=0.34). For the cardiovascular endpoint, there was a lower risk of no aspirin relative to DAPT in the no PPI subgroup (0.41% vs. 3.27%; HR 0.13; 95% CI 0.03–0.60), but not in the PPI subgroup (HR 1.29; 95% CI 0.86–1.93) with a significant interaction (P interaction=0.005). Conclusions: There was no interaction for bleeding between PPI prescription and antiplatelet regimen, but a significant interaction for cardiovascular events, requiring cautious interpretation due to the small no-PPI subgroup and baseline imbalances.

Discussion

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Cite This Study

Nishio et al. (2026) conducted an RCT in Acute coronary syndrome or high bleeding risk undergoing percutaneous coronary intervention (n=5,654). Aspirin-free strategy (prasugrel monotherapy) vs. Dual antiplatelet therapy (aspirin 81-100 mg/day + prasugrel 3.75 mg/day) was evaluated on Co-primary cardiovascular endpoint (composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) in the no-PPI subgroup (HR 0.13, 95% CI 0.03-0.60, p=0.01). An aspirin-free strategy with prasugrel monotherapy significantly reduced the risk of cardiovascular events compared to dual antiplatelet therapy in patients not receiving proton-pump inhibitors (HR 0.13), with a significant interaction between PPI use and antiplatelet regimen.

synapsesocial.com/papers/6a5b3a7a8167787360d24f9d https://doi.org/10.1253/circrep.cr-26-0156

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One-Month Outcomes of Aspirin-Free Strategy for Percutaneous Coronary Intervention With or Without Proton-Pump Inhibitors　― A Post Hoc Subgroup Analysis of STOPDAPT-3 ―

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

One-Month Outcomes of Aspirin-Free Strategy for Percutaneous Coronary Intervention With or Without Proton-Pump Inhibitors　― A Post Hoc Subgroup Analysis of STOPDAPT-3 ―

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading

One-Month Outcomes of Aspirin-Free Strategy for Percutaneous Coronary Intervention With or Without Proton-Pump Inhibitors ― A Post Hoc Subgroup Analysis of STOPDAPT-3 ―

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

One-Month Outcomes of Aspirin-Free Strategy for Percutaneous Coronary Intervention With or Without Proton-Pump Inhibitors ― A Post Hoc Subgroup Analysis of STOPDAPT-3 ―

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading

One-Month Outcomes of Aspirin-Free Strategy for Percutaneous Coronary Intervention With or Without Proton-Pump Inhibitors　― A Post Hoc Subgroup Analysis of STOPDAPT-3 ―

One-Month Outcomes of Aspirin-Free Strategy for Percutaneous Coronary Intervention With or Without Proton-Pump Inhibitors　― A Post Hoc Subgroup Analysis of STOPDAPT-3 ―