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).

What question did this study set out to answer?

This analysis investigates the impact of proton-pump inhibitors on aspirin-free strategies compared to dual antiplatelet therapy after percutaneous coronary intervention.

July 18, 2026Circulation Reports0 citationsOpen Access

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 ―

RNRyota Nishio HWHirotoshi Watanabe TMTakeshi Morimoto

Key Result

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.

Key Points

This analysis investigates the impact of proton-pump inhibitors on aspirin-free strategies compared to dual antiplatelet therapy after percutaneous coronary intervention.
Analyzed data from 5,654 patients discharged within 30 days post-randomization from the STOPDAPT-3 trial.
Categorized patients into PPI (4,958) and no-PPI (696) subgroups for analysis based on antiplatelet regimens.
Evaluated co-primary endpoints for bleeding and cardiovascular events.
No significant interaction between PPI use and bleeding occurred (P=0.34).
Lower risk of cardiovascular events in the no-PPI subgroup (0.41% vs. 3.27%; HR 0.13; 95% CI 0.03–0.60).
A significant interaction for cardiovascular events was noted in the PPI subgroup (HR 1.29; 95% CI 0.86–1.93, P interaction=0.005).

Study Design

Type

RCT (n=5,654)

Blinding

Open-label

Randomization

1:1

Multicenter

Yes

Structured PICO

Does proton-pump inhibitor prescription interact with the early effects of an aspirin-free strategy compared with DAPT after PCI?

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.

Intervention

Aspirin-free strategy (no-aspirin group) with or without proton-pump inhibitors (PPI)

Comparator

Dual antiplatelet therapy (DAPT) with or without proton-pump inhibitors (PPI)

Outcome

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

In patients undergoing PCI, PPI prescription significantly interacts with the cardiovascular effects of an aspirin-free strategy versus DAPT, though this requires cautious interpretation due to subgroup imbalances.

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.

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.

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