Antiplatelet monotherapy maintenance strategies after percutaneous coronary intervention in patients with coronary artery disease at high bleeding risk: a network meta-analysis

Background The optimal antiplatelet monotherapy maintenance strategy after percutaneous coronary intervention (PCI) remains uncertain in patients with coronary artery disease at high bleeding risk, particularly among those not receiving oral anticoagulant therapy. We performed a network meta-analysis to compare the safety and efficacy of different antiplatelet monotherapy strategies after an ultrashort course of dual antiplatelet therapy (DAPT). Methods We searched PubMed, Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials from database inception to July 1, 2026. Randomized controlled trials and subgroup analyses of randomized trials were eligible if they enrolled high bleeding risk patients undergoing PCI who were not receiving oral anticoagulant therapy and compared antiplatelet monotherapy strategies with DAPT or with another monotherapy strategy. The primary safety outcome was BARC major bleeding, and the primary efficacy outcome was major adverse cardiovascular events (MACE). Secondary outcomes included myocardial infarction, all-cause death, and stroke. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a frequentist random-effects network meta-analysis. Results All six included studies informed the drug-specific network meta-analysis. Compared with DAPT, the ORs for major bleeding were 0.26 (95% CI, 0.05–1.42) for aspirin, 0.28 (95% CI, 0.07–1.15) for clopidogrel, and 0.42 (95% CI, 0.17–1.08) for ticagrelor monotherapy. All three confidence intervals were wide and compatible with both lower and higher odds of major bleeding. No significant differences were observed for MACE, all-cause death, or stroke. The higher MI estimates for clopidogrel and aspirin require cautious interpretation given the sparse network and indirect evidence. Conclusions In patients at high bleeding risk undergoing PCI who were not receiving oral anticoagulant therapy, the available evidence was insufficient to determine whether antiplatelet monotherapy after ultrashort DAPT reduces major bleeding compared with DAPT. Ticagrelor monotherapy showed numerically favorable estimates for MACE and major bleeding compared with DAPT, but neither comparison reached statistical significance. However, the sparse evidence network and low certainty of evidence warrant cautious interpretation. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261448916 , PROSPERO CRD420261448916.