Prasugrel-, ticagrelor-, or clopidogrel-based dual antiplatelet therapy after acute coronary syndrome: a frequentist network meta-analysis
Abstract
Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor inhibitor (P2Y12i), remains the cornerstone of secondary prevention of thrombotic complications after acute coronary syndrome (ACS). However, the optimal P2Y12i to use as part of DAPT in patients with ACS remains uncertain. We aimed to perform a frequentist network meta-analysis comparing 1-year DAPT strategies based on different P2Y12 inhibitors after ACS. PubMed, Scopus, and Cochrane databases were searched from inception through January 2026 for randomised controlled trials (RCTs). Outcomes of interest were major adverse cardiovascular events (MACE), all-cause mortality, cardiac death, major bleeding, myocardial infarction (MI), stent thrombosis, and stroke. Random effects models were used to generate risk ratios (RRs) with 95% confidence intervals (CIs). Treatments were ranked using the surface under the cumulative ranking (SUCRA). Thirteen RCTs comprising 54,215 patients were included (clopidogrel-based DAPT: n=23,557; ticagrelor-based DAPT: n=14,245; prasugrel-based DAPT: n=16,413). Compared with clopidogrel-based DAPT, prasugrel-based DAPT significantly reduced cardiac death (RR 0.89; 95% CI 0.80–1.00), MI (RR 0.85; 95% CI 0.72–0.99), and stent thrombosis (RR 0.49; 95% CI 0.38–0.62). Ticagrelor-based DAPT reduced cardiac death (RR 0.84; 95% CI 0.75–0.94) and stent thrombosis (RR 0.72; 95% CI 0.58–0.89) compared with clopidogrel-based DAPT. Major bleeding was lower with clopidogrel-based DAPT compared with ticagrelor-based DAPT (RR 0.79; 95% CI 0.66–0.95). SUCRA analysis ranked prasugrel-based DAPT as most effective for reducing MACE (0.94), MI (0.95), stent thrombosis (0.99), and stroke (0.79). Ticagrelor-based DAPT ranked highest for reducing all-cause mortality (0.74) and cardiac death (0.90), while clopidogrel-based DAPT ranked highest for minimizing major bleeding (0.96). Among 1-year DAPT strategies following ACS, prasugrel-based DAPT appears to provide the most favorable balance in reducing ischemic outcomes without a significant increase in major bleeding.Figure