Key result
Prasugrel-based DAPT cuts cardiac death ~11% vs clopidogrel post-ACS, with fewer MIs and stent thromboses.
Why the study?
Although DAPT with aspirin and a P2Y12 receptor inhibitor is the cornerstone of secondary prevention after ACS, the optimal P2Y12i to use as part of DAPT in patients with ACS remained uncertain.
Does prasugrel- or ticagrelor-based 1-year dual antiplatelet therapy reduce major adverse cardiovascular events, mortality, ischemic outcomes, and major bleeding compared with clopidogrel-based DAPT in patients after acute coronary syndrome?
Meta-Analysis (n=54,215)
Randomized controlled trials included
Does prasugrel- or ticagrelor-based 1-year dual antiplatelet therapy reduce major adverse cardiovascular events, mortality, ischemic outcomes, and major bleeding compared with clopidogrel-based DAPT in patients after acute coronary syndrome?
In a network meta-analysis of 54,215 patients with acute coronary syndrome, 1-year prasugrel-based DAPT provided the most favorable balance in reducing ischemic events (MACE, MI, stent thrombosis, and stroke) without a significant increase in major bleeding, while ticagrelor ranked highest for mortality reduction and clopidogrel ranked highest for minimizing major bleeding.
Supports prasugrel-based DAPT post-ACS to reduce ischemic events; extends network meta-analysis ranking of potent P2Y12 inhibitors.
Introduction 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. Purpose We aimed to perform a frequentist network meta-analysis comparing 1-year DAPT strategies based on different P2Y12 inhibitors after ACS. Methods 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). Results 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). Conclusion 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.
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Joseph et al. (2026) conducted a meta-analysis in Acute coronary syndrome (n=54,215). Prasugrel-based or ticagrelor-based dual antiplatelet therapy vs. Clopidogrel-based dual antiplatelet therapy was evaluated on Cardiac death (alongside MACE, all-cause mortality, major bleeding, myocardial infarction, stent thrombosis, and stroke) (RR 0.89, 95% CI 0.80-1.00). Prasugrel-based DAPT reduced cardiac death (RR 0.89; 95% CI 0.80-1.00), MI (RR 0.85), and stent thrombosis (RR 0.49) vs clopidogrel-based DAPT after ACS.
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