Optimal time for aspirin withdrawal after PCI in ACS: a pairwise and network meta-analysis with time to event data of...

In patients with ACS undergoing PCI, de-escalation to P2Y12-inhibitor monotherapy reduces bleeding, but the optimal timing of aspirin withdrawal is uncertain. We conducted pairwise and network meta-analyses of randomized trials comparing P2Y12-inhibitor monotherapy after aspirin discontinuation versus dual antiplatelet therapy (DAPT) in ACS post-PCI. Random-effects models were used. The network meta-analysis (NMA) compared four strategies (12-month DAPT [central comparator]; aspirin stop < 1 month, 1-2 months, or 3 months) and ranked treatments using SUCRA. (PROSPERO ID: CRD420251151605). A total of 33,292 participants from 10 RCTs were included. In the pairwise meta-analysis, monotherapy reduced net adverse clinical events (NACE) (5.1% vs. 6.7%; RR: 0.75; 95% CI: 0.65-0.86) and bleeding, including clinically relevant bleeding (RR: 0.45; 95% CI: 0.39-0.53) and major bleeding (RR: 0.47; 95% CI: 0.37-0.60). In the NMA, aspirin discontinuation at 3 months showed a trend toward lower NACE versus 12-month DAPT (RR 0.66; 95% CI 0.42-1.04) and ranked most favorable for net and ischemic outcomes (NACE, MI, MACCE, and all-cause mortality), although estimates for individual ischemic endpoints were imprecise and not statistically different from 12-month DAPT. Aspirin discontinuation at < 1 month showed an unfavorable mortality ranking, with a concordant meta-regression signal suggesting higher mortality with earlier aspirin withdrawal. De-escalation to P2Y₁₂ inhibitor monotherapy after PCI in ACS reduced NACE, mainly by lowering bleeding. In network analyses, aspirin discontinuation at 3 months ranked most favorable for net and ischemic outcomes, whereas discontinuation at < 1 month showed an unfavorable mortality signal.