Prasugrel lowered the risk of MACE compared with clopidogrel (OR 0.80; 95% CI 0.69-0.93) and ticagrelor (OR 0.83; 95% CI 0.70-0.98) in patients after percutaneous coronary intervention.
Meta-Analysis (n=48,904)
Does prasugrel or ticagrelor improve efficacy and safety outcomes compared to clopidogrel in patients undergoing percutaneous coronary intervention?
In patients undergoing PCI, prasugrel provides a superior balance of efficacy and safety compared to both ticagrelor and clopidogrel, significantly reducing MACE without the increased bleeding risk seen with ticagrelor.
Effect estimate: OR 0.80 (95% CI 0.69-0.93)
Importance: The relative efficacy and safety of oral P2Y purinergic receptor 12 (P2Y12) inhibitors (clopidogrel, ticagrelor, or prasugrel) after percutaneous coronary intervention (PCI) are not well defined. Objective: To assess the efficacy and safety of oral P2Y12 inhibitors in patients who underwent PCI. Data Sources and Study Selection: PubMed and Embase were searched until November 15, 2025, for randomized clinical trials comparing at least 2 of the 3 agents. Data Extraction and Synthesis: Data were abstracted by 2 independent authors according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Random-effects odds ratios (ORs) and 95% confidence intervals were calculated. Data were analyzed in December 2025. Main Outcomes and Measures: The primary efficacy outcome was major adverse cardiovascular events (MACE), while the primary safety outcome was major bleeding. The primary analysis compared prasugrel and ticagrelor in reference to clopidogrel using a mixed treatment comparison meta-analysis. Results: Data were analyzed from 15 randomized clinical trials that included 48 904 patients (mean SD age, 63.2 4.21 years; 13 330 female patients 27.3%). Compared with clopidogrel, there was a lower risk of MACE (OR, 0.80; 95% CI, 0.69-0.93) driven by lower myocardial infarction (OR, 0.71; 95% CI, 0.62-0.82) and stent thrombosis (OR, 0.48; 95% CI, 0.37-0.62) with prasugrel. MACE was not reduced with ticagrelor compared with clopidogrel, although there was lower stent thrombosis (OR, 0.73; 95% CI, 0.59-0.91). Furthermore, there was lower risk of MACE with prasugrel compared to ticagrelor (OR, 0.83; 95% CI, 0.70-0.98) driven by lower myocardial infarction (OR, 0.78; 95% CI, 0.65-0.94) and stent thrombosis (OR, 0.66; 95% CI, 0.49-0.88). There was a higher risk of major bleeding with ticagrelor vs clopidogrel (OR, 1.24; 95% CI, 1.01-1.52) driven by higher intracranial hemorrhage (OR, 1.89; 95% CI, 1.08-3.33). Prasugrel ranked first, followed by ticagrelor and clopidogrel, for MACE, myocardial infarction, and stent thrombosis. Conclusions and Relevance: In this systematic review and meta-analysis of 15 randomized clinical trials in patients who underwent PCI, prasugrel provided the optimal balance between efficacy and safety compared with ticagrelor and clopidogrel.
This large meta-analysis published in JAMA Cardiology suggests that prasugrel offers the best balance of efficacy and safety among oral P2Y12 inhibitors after PCI. The findings are generating significant discussion about the optimal antiplatelet therapy in this setting.
Maqsood et al. (Wed,) conducted a meta-analysis in Percutaneous coronary intervention (PCI) (n=48,904). Prasugrel or ticagrelor vs. Clopidogrel was evaluated on Major adverse cardiovascular events (MACE) (OR 0.80, 95% CI 0.69-0.93). Prasugrel lowered the risk of MACE compared with clopidogrel (OR 0.80; 95% CI 0.69-0.93) and ticagrelor (OR 0.83; 95% CI 0.70-0.98) in patients after percutaneous coronary intervention.