# Early aspirin withdrawal versus dual antiplatelet therapy in high-risk patients after percutaneous coronary intervention: Meta-analysis of randomized trials

## TL;DR

Stopping aspirin within 3 months after a heart stent procedure reduces bleeding without increasing heart attacks in high-risk patients, but stopping it immediately is risky.

## Contribution

This study provides evidence that early aspirin withdrawal (within 3 months) is safer than immediate cessation in high-risk post-PCI patients.

## Key findings

- P2Y12-inhibitor monotherapy reduced bleeding without increasing myocardial infarction.
- Immediate aspirin withdrawal increased MI risk, while early discontinuation did not.
- Bayesian analyses showed high probabilities of bleeding benefit and MI safety with 3-month aspirin discontinuation.

## Abstract

Patients at high ischemic or bleeding risk after percutaneous coronary intervention (PCI) require protection against thrombotic events with dual antiplatelet therapy (DAPT) while avoiding bleeding. Although guidelines recommend 12-month DAPT after acute coronary syndrome (ACS), recent trials have tested the safety of early aspirin withdrawal with potent P2Y12-inhibitor monotherapy.

We performed a meta-analysis of randomized trials (from inception through August 2025) comparing early aspirin withdrawal (≤3 months) with transition to ticagrelor- or prasugrel-monotherapy versus continued DAPT. Co-primary outcomes were myocardial infarction (MI) and clinically relevant bleeding. Prespecified timing analyses stratified the comparison versus DAPT by aspirin timing: immediate (aspirin noninitiation or in-hospital cessation) and early (post-discharge discontinuation within 3 months). Bayesian models quantified risk-stratified probabilities of benefit and harm; trial sequential analysis (TSA) assessed conclusiveness of evidence. Seven trials (n = 27,743) were included. P2Y12-inhibitor monotherapy reduced bleeding (HR = 0.55, 95% CI [0.42, 0.71]; p < 0.001) without significantly increasing MI overall (HR = 1.11, 95% CI [0.91, 1.35]; p = 0.31), death, stroke, or stent thrombosis. Immediate aspirin noninitiation/cessation increased MI (HR = 1.41, 95% CI [1.01, 1.97]; p = 0.04), whereas early discontinuation did not (HR = 0.97, 95% CI [0.76, 1.24]; p = 0.82). TSA indicated conclusiveness for bleeding benefit and futility for an MI excess. Analyses restricted to ACS confirmed the overall results. Bayesian analyses corroborated these effects and identified risk-aligned timing: in high bleeding risk, ≤1-month aspirin discontinuation yielded a 100% posterior probability of bleeding benefit (NNT = 12) and 70% probability of MI-safety; in high ischemic risk, 3-month aspirin discontinuation yielded 100% probability of bleeding benefit (NNT = 57) and 86% probability of MI-safety. Limitations include aggregate data only and limited precision for the immediate aspirin withdrawal subgroup.

Among high-risk post-PCI patients on ticagrelor/prasugrel, discontinuing aspirin within 3 months reduces bleeding without an ischemic trade-off versus DAPT. Immediate aspirin noninitiation or cessation should be avoided; timing should be individualized to bleeding and ischemic risk. PROSPERO: CRD420251167706.

After a coronary stent procedure, patients take two antiplatelet medicines to reduce the risk of ischemic events, but this can increase bleeding.

Many patients are at higher risk of ischemic events or bleeding than lower-risk patients after percutaneous coronary intervention, so doctors need safer ways to balance these two risks. Several trials have tested stopping aspirin early and continuing only the other antiplatelet medicine, but the safest timing—especially in high-risk patients—has been uncertain.

We performed a meta-analysis of 7 randomized clinical trials including 27,743 high-risk patients after a stent procedure.

Overall, stopping aspirin within 3 months and continuing a potent antiplatelet medicine reduced bleeding compared with staying on two medicines, without a clear increase in myocardial infarction (MI), death, or stroke.

However, not starting aspirin or stopping it immediately in hospital was linked to more MI than continuing two medicines.

For many high-risk patients after a stent procedure, stopping aspirin within the first 1–3 months while continuing the other antiplatelet medicine may lower bleeding risk without increasing MI overall.

Stopping aspirin right away may be risky and should generally be avoided; decisions about timing should be made with the treating clinician based on the patient’s bleeding and ischemic risk.

A limitation of this study is that our conclusions are based on summary results reported in published trials, not individual-patient data, and only a few studies tested stopping aspirin immediately, so those specific results should be considered hypothesis-generating.

In a meta-analysis, Eliano Navarese and colleagues investigate the effect of early aspirin withdrawal after a percutaneous coronary intervention on risk of myocardial infarction and bleeding using data from randomized trials