Real-World Evidence from an Emulated Randomized Controlled Trial Supports Superior Efficacy of Prasugrel over Ticagrelor in Acute Coronary Syndromes

Nils Krüger (München)1, J. Krefting (München)1, T. Keßler (München)1, R. S. Schmieder (München)1, F. Starnecker (München)1, A. Dutsch (München)1, C. Gräßer (München)1, U. Meyer-Lindemann (München)2, T. Storz (München)2, I. Pugach (München)2, U. Güldener (München)2, A. Kastrati (München)1, S. Cassese (München)3, H. Schunkert (München)1, M. von Scheidt (München)1

1Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; 2Deutsches Herzzentrum München Erwachsenenkardiologie München, Deutschland; 3Deutsches Herzzentrum München München, Deutschland


Background: In patients with acute coronary syndrome (ACS) undergoing invasive strategy, current guidelines recommend treatment with either ticagrelor or prasugrel for 1 year. The ISAR-REACT 5 randomized controlled trial (IR5 RCT) demonstrated prasugrel's superior efficacy in reducing the primary outcome all-cause mortality, myocardial infarction, or stroke, with comparable safety outcome in bleeding. This study emulated the IR5 RCT in German health claims data.

Methods: Emulation of inclusion and exclusion criteria from the IR5 RCT led to 15,866 propensity score matched individuals with interventionally-treated ACS on ticagrelor or prasugrel. Analyses were conducted for endpoints defined as in the RCT. Subsequently, a comparison of the results from this real-world evidence (RWE) study and the RCT was conducted. Additionally, subgroup analyses of the individual ACS components ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina (UA) were conducted.

Findings: The primary endpoint occurred in 9.1% of ticagrelor and 7.0% of prasugrel treated individuals (hazard ratio 1.31, 95% confidence interval 1.17-1.46; P<0.001). Except all-cause mortality (HR 1.13; CI 0.85-1.49; P=NS), all other secondary endpoints (MI, stroke, stent thrombosis) occurred significantly more often in the ticagrelor arm. The safety outcome bleeding revealed no significant drug differences. Subgroup analysis revealed superiority for prasugrel particularly in individuals with STEMI and NSTEMI, but not UA. Statistically, test results and hazard ratios of this emulated study were in agreement with the data from IR5 RCT.

Interpretation: This real-world evidence study supports superior efficacy of prasugrel over ticagrelor in individuals with ACS without increased risk of bleeding. With nearly four times the cohort size of the IR5 RCT, this RWE study helps address efficacy and safety in ACS subgroups, further supporting prasugrel's preference over ticagrelor in guideline recommendations.

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