Ticagrelor versus clopidogrel in STEMI post-PCI: A mixed-design meta-analysis of efficacy and safety
Background: ST-segment elevation myocardial infarction (STEMI) requires primary percutaneous coronary intervention (PCI) and dual antiplatelet therapy with aspirin and a purinergic receptor Y12 inhibitor to reduce thrombotic risks. Ticagrelor, a potent purinergic receptor Y12 inhibitor, offers faster and stronger platelet inhibition than clopidogrel, but evidence on its efficacy and safety in STEMI patients post-PCI is conflicting. This study aims to compare the efficacy and safety of ticagrelor versus clopidogrel in STEMI patients undergoing primary PCI. Methods: This systematic review and meta-analysis, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, searched PubMed, Embase, ScienceDirect, and ClinicalTrials.gov up to July 2025. Included were randomized controlled trials and observational studies comparing ticagrelor to clopidogrel in adult STEMI patients post-PCI, reporting cardiovascular outcomes. Data were pooled using odds ratios (ORs) with 95% confidence intervals (CIs) via random-effects models. Results: Eight studies (5 randomized controlled trials, 3 observational; n = 31,729) showed ticagrelor significantly reduced all-cause mortality (OR = 0.64, 95% CI = 0.47–0.88; P = .006), cardiovascular mortality (OR = 0.68, 95% CI = 0.60–0.93; P = .01), major adverse cardiovascular events (OR = 0.71, 95% CI = 0.60–0.84; P = .01), myocardial infarction (OR = 0.71, 95% CI = 0.61–0.83; P < .00001), stent thrombosis (OR = 0.66, 95% CI = 0.55–0.79; P < .00001), and major bleeding (OR = 0.87, 95% CI = 0.78–0.97; P = .01), but increased target vessel revascularization (OR = 1.30, 95% CI = 1.05–1.61; P = .02). No significant difference was observed in stroke risk (OR = 1.16, 95% CI = 0.89–1.52; P = .28). Conclusion: Ticagrelor outperforms clopidogrel in STEMI post-PCI, reducing key adverse outcomes, though higher target vessel revascularization risk warrants caution.