Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care
Authors: Krüger Nils , Krefting Johannes , Kessler Thorsten , Schmieder Raphael , Starnecker Fabian , Dutsch Alexander , Graesser Christian , Meyer-Lindemann Ulrike , Storz Theresa , Pugach Irina , Frieß Christian , Chen Zhifen , Bongiovanni Dario , Manea Iulian , Dreischulte Tobias , Offenborn Frank , Krase Peter , Sager Hendrik B. , Wiebe Jens , Kufner Sebastian , Xhepa Erion , Joner Michael , Trenkwalder Teresa , Gueldener Ulrich , Kastrati Adnan , Cassese Salvatore , Schunkert Heribert , von Scheidt Moritz ,   DigiMed Bayern Consortium, Adam Jonathan , Anselm Reiner , Ates Sara , Bauer Sabine , Beck Nicole , Beckmann Jürgen , Berutti Riccardo , Brandmaier Stefan , Bruun Tim , Cassese Salvatore , Decker Manuela , Dichgans Martin , Diesselhorst Philine , Domdey Horst , Doppler Stefanie , Dreßen Martina , Dressler Arne , Dufour Florent , Duscha Sven , Eckstein Hans H. , Farzeen Aiman , Feiler Therese , Friess Christian , Gall Ines , Gassner Ulrich M , Gieger Christian , Gotor-Blazquez Monica , Gueldener Ulrich , Hammer Nicolay , Hawe Johann , Heidel Verena , Hendel Thomas , Holdenrieder Stefan , Jonas Stephan , Kameric Muamer , Kastrati Adnan , Kessler Thorsten , Knoedlseder Katharina , Koenig Wolfgang , Kohlmayer Florian , Krane Markus , Kranzelmueller Dieter , Krefting Johannes , Krüger Nils , Kroke Anja , Lahm Harald , Lange Ruediger , Lehmann Andreas , Li Ling , Linkohr Birgit , Maegdefessel Lars , Mann Matthias , Malik Rainer , Meitinger Thomas , Neb Irina , O'Hehir Tina , Pang Shichao , Perl Benedikt , Peters Annette , Peymani Fatemeh , Pichler Roland , Pfister Heiko , Pisano Paola , Prokisch Holger , Pugach Irina , Reimer Lara M , Sander Michaela , Sanin Veronika , Schlieben Lea D. , Schlote Yannick , Schmid Sofie , Schmieder Raphael S. , Schunkert Heribert , Schwab Marius , Sharikadze Megi , Sinha Ankit , Starnecker Fabian , Steger Medini , Steigerwald Sophia , Sun Ruoyu , von Scheidt Moritz , Wagner Matias , Westerlund Annie , Wiehler Jens , Wierer Michael , Zinterhof Peter 
Published: December 2024

ImportanceIn patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. The ISAR-REACT5 randomized clinical trial demonstrated superiority for prasugrel, although concerns were raised about the generalizability of some underpowered subgroup analyses.ObjectivesTo emulate a randomized clinical trial evaluating the safety and effectiveness of ticagrelor vs prasugrel under the conditions of routine care in individuals with ACS planned to undergo an invasive treatment strategy.Design, Setting, and ParticipantsThis new-user cohort study included secondary data from a German statutory health insurance claims database between January 2012 and December 2021, using 1:1 propensity score nearest-neighbor matching to emulate ISAR-REACT5. Individuals with ACS receiving either ticagrelor or prasugrel treatment after hospital discharge were followed up for 1 year. Eligibility criteria closely emulated those of ISAR-REACT5 and included age of 18 years or older and cardiovascular risk factors. Data were analyzed from May 2023 to May 2024.ExposureOutpatient prescription of ticagrelor or prasugrel.Main Outcomes and MeasuresThe primary end point was the composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year of outpatient treatment initiation. Secondary end points included individual components of the primary end point and stent thrombosis. The safety end point was major bleeding. A Cox proportional hazards regression model was fitted to the overall cohort.ResultsOf 17 642 propensity score–matched individuals (mean [SD] age, 63.1 [10.9] years; 73.9% male), 8821 received ticagrelor and 8821 received prasugrel. Agreement was met in 11 of 12 predefined agreement metrics when comparing the results with ISAR-REACT5. The primary composite end point of all-cause mortality, MI, or stroke occurred in 815 individuals (9.2%) receiving ticagrelor and 663 (7.5%) receiving prasugrel (hazard ratio [HR], 1.24; 95% CI, 1.12-1.37). Myocardial infarction (HR, 1.20; 95% CI, 1.06-1.36) and stroke (HR, 1.33; 95% CI, 1.02-1.74) each occurred significantly more often in the ticagrelor group. Analysis of all-cause mortality (HR, 1.27; 95% CI, 0.99-1.64), stent thrombosis (HR, 1.11; 95% CI, 0.89-1.30), and major bleeding (HR, 1.12; 95% CI, 0.96-1.32) revealed no significant differences between treatment groups. Subgroup analysis showed that prasugrel was associated with the primary composite end point in fewer individuals with ST-segment elevation MI (338 of 4941 [6.8%] vs 451 of 4852 [9.3%]).Conclusions and RelevanceThis cohort study found that prasugrel was associated with lower rates of all-cause mortality, MI, or stroke compared with ticagrelor in individuals with ACS undergoing an invasive treatment strategy in routine care, particularly in individuals with ST-segment elevation MI. The findings suggest that carefully designed database studies can complement and extend findings from randomized clinical trials, informing guidelines and clinical decision-making.