by Eliano P. Navarese, Paul Gurbel, Udaya Tantry, Giuseppe Talanas, Klaudyna Grzelakowska, Julia Umińska, Young-Hoon Jeong, Kevin Bliden, Safi U. Khan, Jacek Kubica, Timothy D. Henry, Michael E. Farkouh, Dean J. Kereiakes Background 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. Methods and findings 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 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. Conclusions 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.
by Eliano P. Navarese, Paul Gurbel, Udaya Tantry, Giuseppe Talanas, Klaudyna Grzelakowska, Julia Umińska, Young-Hoon Jeong, Kevin Bliden, Safi U. Khan, Jacek Kubica, Timothy D. Henry, Michael E. Farkouh, Dean J. Kereiakes Background 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. Methods and findings 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 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. Conclusions 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.