The efficacy and safety of ticagrelor and prasugrel versus clopidogrel in post-PCI dual antiplatelet therapy in chronic coronary syndrome: a systematic review and meta-analysis

Clopidogrel is the guideline-recommended P2Y12 inhibitor for dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) in Chronic Coronary Syndrome (CCS). Recent evidence suggests potential benefits of more potent P2Y12 inhibitors, primarily Ticagrelor, though their role in CCS remains less defined than in acute settings. To compare the efficacy and safety of Ticagrelor or Prasugrel with Clopidogrel in DAPT following PCI in CCS patients. A systematic approach was used to identify eligible randomized controlled trials (RCTs) and observational studies comparing the safety and efficacy of Ticagrelor or Prasugrel versus Clopidogrel. A meta-analysis using a random-effects model evaluated major adverse cardiovascular events (MACE), its individual components, and bleeding outcomes. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by study design, P2Y12 inhibitor type, follow-up duration, and geographical region. Twelve studies (6 RCTs, 6 observational) were included, comprising 10,048 patients receiving potent P2Y12 inhibitors (Ticagrelor: 10 studies; Prasugrel: 3 studies) and 45,103 receiving Clopidogrel. Potent P2Y12 inhibitors were associated with a significantly reduced risk of MACE (OR = 0.69, 95% CI: 0.55–0.88) and all-cause mortality (OR = 0.63, 95% CI: 0.46–0.88). These benefits were primarily driven by the Ticagrelor subgroup, observational data, follow-up > 6 months, and Asian studies. While no significant differences were found for myocardial infarction, stroke, or overall stent thrombosis, the Ticagrelor subgroup showed a significantly lower risk of revascularization (OR = 0.67, 95%CI: 0.52–0.86). Regarding safety, while major bleeding showed a non-significant trend toward increase (OR = 1.41, 95% CI: 0.92–2.17), minor bleeding was significantly higher in the potent P2Y12 group (OR = 1.56, 95% CI: 1.26–1.95). This meta-analysis suggests that intensified DAPT, primarily Ticagrelor-based, may offer superior clinical benefit to Clopidogrel-based DAPT in patients with CCS undergoing PCI, particularly by reducing MACE, all-cause mortality, and revascularization. However, these benefits are accompanied by an increased risk of minor bleeding and a potential signal toward higher major bleeding. Considering the scarcity of large-scale RCTs, heterogeneous MACE definitions, limited data on Prasugrel, and ethnic/racial influence on bleeding risk and thrombotic events, these findings emphasize the need for individualized post-PCI antiplatelet regimens and support further long-term RCTs to better define the role of potent P2Y12 inhibitors in this population.