Real-world evidence supports superior efficacy of prasugrel over ticagrelor in individuals with acute coronary syndrome

Abstract Background In patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. Preference for one of the two drugs is under debate although the ISAR-REACT5 trial revealed advantages for prasugrel. This real-world data study evaluated the efficacy and safety of ticagrelor versus prasugrel in individuals with ACS undergoing invasive treatment by emulating a target trial analogous to ISAR-REACT5. Methods Following the Population, Intervention, Comparator, Outcome, and Timing (PICOT) framework, within a German health claims database, we adapted the inclusion and exclusion criteria from ISAR-REACT5 and identified a 1:1 propensity score-matched cohort with ACS being treated after hospital discharge with either ticagrelor or prasugrel (n=9,380, each). End points were defined as in ISAR-REACT5 at 1-year follow-up. Additionally, subgroup analyses of individual ACS components ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina (UA) were conducted. Results The primary composite end point occurred in 9.2% of ticagrelor and 7.4% of prasugrel treated individuals (hazard ratio 1.22; 95% confidence interval 1.10-1.35). Likewise, the secondary end points MI and stroke occurred significantly more often in the ticagrelor arm. All-cause mortality, stent thrombosis, and the safety end point bleeding revealed no significant differences. Subgroup analysis revealed superiority for prasugrel particularly in individuals with STEMI. Statistically, test results and hazard ratios of this real-world data study were in agreement with the findings of ISAR-REACT5. Conclusions With over four times the cohort size of ISAR-REACT5, this study indicates superior efficacy of prasugrel over ticagrelor in individuals with ACS undergoing invasive strategy.Cumulative incidence of primary endpointGraphical abstract