A multinational retrospective cohort study across seven claims and EHR databases—ultimately drawing on 133,718 ACS patients who underwent percutaneous coronary intervention across Korean and U.S. commercial databases—found no statistically credible difference between ticagrelor and prasugrel for 1-year MACE (pooled HR 1.28, 95% CrI 0.89–1.88). Secondary endpoints including all-cause mortality, hemorrhagic events, stroke, and gastrointestinal bleeding similarly showed no credible between-drug differences, though point estimates consistently trended toward higher risk with ticagrelor.
This finding lands in a persistently contested space. Head-to-head randomized trial data comparing these two agents remain limited—most landmark evidence tested each drug against clopidogrel separately—leaving clinicians to navigate guideline nuance without direct comparative certainty. The absence of a credible difference supports equipoise in drug selection, though the post-hoc U.S.-only analysis (HR 1.49, CrI 1.05–2.10 for MACE) introduces a signal that warrants scrutiny: it suggests population-level heterogeneity may obscure meaningful subgroup differences. Only three of seven databases survived prespecified diagnostic thresholds, indicating residual confounding concerns in observational data of this kind. Prasugrel's contraindications in prior stroke patients and the elderly already limit its use, so real-world populations likely differ systematically. This is a preprint not yet peer-reviewed, and the substantial between-database heterogeneity means conclusions could shift materially. Incremental rather than paradigm-shifting, this study nonetheless provides the largest propensity-adjusted comparative evidence base to date.