Ticagrelor vs prasugrel for acute coronary syndrome in routine care

Importance In 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. Objectives To 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 Participants This 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. Exposure Outpatient prescription of ticagrelor or prasugrel. Main Outcomes and Measures The 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. Results Of 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% ...