Time- and risk-dependent effects of dual antiplatelet therapy targeting the P2Y12 receptor after CABG: A network meta-analysis of graft permeability and clinical outcomes

The optimal anticoagulation strategy following Coronary artery bypass grafting remains undetermined, particularly regarding the balance between graft patency, ischemic events, and bleeding across different follow-up periods and risk profiles. A systematic search was conducted in PubMed, Embase, Web of Science, and the Cochrane Database to identify randomized controlled trials comparing regimens of aspirin, DAPT (clopidogrel or ticagrelor), and rivaroxaban. The primary angiographic endpoints were saphenous vein graft(SVG) patency and the left internal mammary artery(LIMA) occlusion; clinical endpoints included myocardial infarction, major adverse cardiovascular events(MACE), major bleeding, and all-cause mortality. A random-effects network meta-analysis was conducted, reporting odds ratios (OR) and 95% CIs, with pre-specified 1-year follow-up stratification and multiple subgroup analyses.The primary analysis included 17 RCTs with 1-year follow-up (9,831 patients). SVG occlusion: Aspirin plus ticagrelor (OR = 0.41,95% CI:0.30–0.56) and aspirin plus clopidogrel (OR = 0.59, 95% CI: 0.44–0.78) were both significantly superior to aspirin monotherapy. MACE: Compared with aspirin monotherapy, no anticoagulation strategy showed a statistically significant difference. Major bleeding: Aspirin plus ticagrelor (OR = 2.53,95% CI:1.59–4.04) and rivaroxaban monotherapy (OR = 2.33, 95% CI: 1.01–5.37) significantly increased the risk. No strategy showed statistically significant differences in myocardial infarction or all-cause mortality. No clear conclusions could be drawn regarding LIMA occlusion due to the rarity of events. Subgroup analysis: In the subgroups of off-pump CABG (OR = 0.42, 95% CI: 0.19–0.90) and early initiation ≤ 48 h (OR = 0.47, 95% CI: 0.29–0.75), the combination of aspirin and ticagrelor significantly reduced MACE; however, the risk of bleeding increased with this regimen when initiation was delayed (> 48 h) (OR = 2.51, 95% CI: 1.52–4.16). Sensitivity analyses showed that the conclusions regarding SVG occlusion and major bleeding were highly robust (the direction and significance of ORs remained consistent across all sensitivity scenarios), whereas estimates for MACE and all-cause mortality were sensitive to specific studies. The net benefit of post-CABG antithrombotic therapy is time- and patient-specific. DAPT (particularly aspirin plus clopidogrel) offers the optimal balance between revascularization protection and bleeding risk; the ticagrelor regimen provides stronger ischemic protection but comes at a higher cost of bleeding; the rivaroxaban regimen is not suitable for routine use. An individualized antithrombotic strategy based on risk stratification is recommended. Graphical Abstract Dual Antiplatelet Therapy After CABG: Better Graft Protection, but at a Bleeding Cost；Graphical Abstract Legend：Study framework and main findings of the network meta‑analysis comparing seven antithrombotic strategies after coronary artery bypass grafting (CABG).Left panel (Clinical Question): After CABG, the optimal antithrombotic strategy remains uncertain. Key outcomes to balance include SVG graft patency, LIMA patency, ischemic events (MACE, myocardial infarction, all‑cause mortality), and major bleeding.Centre panel (Study Design): Network meta‑analysis of 17 randomized controlled trials with 1‑year follow‑up (9,831 patients, Seven treatment strategies were compared in the network meta-analysis: aspirin (ASA) alone, ticagrelor (Tic) alone, clopidogrel (Clop) alone, rivaroxaban (Riva) alone, ASA + ticagrelor, ASA + clopidogrel, and rivaroxaban + ASA.right panel (Key Findings at 1 Year):SVG occlusion – Significantly reduced by aspirin+ticagrelor (OR 0.41, 95% CI 0.30–0.56) and aspirin+clopidogrel (OR 0.59, 95% CI 0.44–0.78)；Ischemic outcomes (MACE, myocardial infarction, all‑cause mortality) – No strategy showed a statistically significant reduction compared with aspirin alone; all confidence intervals crossed 1.0；Major bleeding – Significantly increased by aspirin+ticagrelor (OR 2.53, 95% CI 1.59–4.04) and rivaroxaban alone (OR 2.33, 95% CI 1.01–5.37). Aspirin+clopidogrel did not show a statistically significant increase (OR 1.19, 95% CI 0.57–2.47)；LIMA occlusion – No significant differences were detected, likely due to very low event rates (3.74%).Bottom Panel (Clinical Implications):Overall, while early DAPT improves SVG patency, the 1-year clinical benefit remains neutral, and bleeding risk must be individualized. Rivaroxaban-based strategies are not routinely supported by current evidence. The findings highlight the need for a personalized decision-making approach balancing SVG protection and bleeding risk in post-CABG antithrombotic management.