What Additional Insights Does a Bayesian Network Meta-Analysis Provide? Revisiting P2Y12 Inhibitors After Acute Coronary Syndromes

Background: The optimal P2Y12 inhibitor after percutaneous coronary intervention (PCI) remains debated. A recent frequentist network meta-analysis (NMA) concluded prasugrel provided optimal efficacy-safety balance. We update our previous Bayesian NMA with recent trials and contrast our findings with the frequentist NMA. Methods: We extended our 2023 systematic review by adding two trials published after our search cutoff. The primary efficacy endpoint was a composite of all-cause mortality, a recurrent non-fatal myocardial infarction, or non-fatal stroke (MACE). The primary safety endpoint was study-reported major bleeding events. Bayesian network meta-analysis with a primary binomial complementary log-log model with log(time) offset and random effects was performed. A statistical workflow with prior and posterior predictive checks, convergence diagnostics, model comparisons, sensitivity analyses and probabilities for a range of practical equivalence (ROPE: HR 0.90-1.11) are also reported. Results: 19 RCTs (n = 60,619) were identified. For MACE, prasugrel's probability of a clinical efficacy benefit (hazard ratio (HR) <0.9) was 70% compared to clopidogrel (HR 0.87, 95% credible interval (CrI )0.76-1.03) and 54% compared to ticagrelor. (HR 0.89, 95% CrI 0.73-1.12). For the ticagrelor versus clopidogrel comparison 76% of the posterior probability (HR 0.98, 95%CrI 0.82-1.18) lies in the ROPE. Ticagrelor (HR 1.26, 95%CrI 1.01-1.63) and prasugrel (HR 1.1, 95%CrI 0.88-1.26) showed 86% and 51% probabilities respectively of meaningful bleeding harm (HR > 1.1) versus clopidogrel. Conclusions: Despite 19 RCTs and approximately 60,000 patients, the Bayesian framework revealed clinically important uncertainties and identified probable regions of equivalence among the different P2Y12 inhibitors that were under appreciated with the previous frequentist publication.