Date of Original Version
Background: Observational studies comparing ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have yielded contradictory results, but these studies often did not consider differential censoring (e.g., for treatment switching or insurance disenrollment) or confounding by time‐dependent factors.
Objective: Our objective was to conduct a comparative effectiveness and safety analysis of ticagrelor and prasugrel in patients who underwent PCI after being hospitalized for an ACS.
Methods: This study used the Optum’s de‐identified Clinformatics® Data Mart Database and included patients aged 18 years or older with an index hospital admission between May 2012 and September 2015, a diagnosis of ACS managed with PCI, and treatment with either ticagrelor or prasugrel. The primary composite outcome was defined as the first occurrence of all‐cause death, myocardial infarction (MI), or ischemic stroke. The secondary composite outcome included the first occurrence of gastrointestinal (GI) bleed, intracranial hemorrhage (ICH), or other major bleeds requiring hospitalization. Weighted Cox proportional hazard models and robust variance estimation were implemented to adjust for baseline comorbidities, time‐varying exposure, time‐dependent confounders, and differential censoring.
Results: Included in the analysis were 2,559 patients initiated on ticagrelor and 4,456 patients initiated on prasugrel following PCI. Patients initiated on ticagrelor were 10% more likely to have eligibility disenrollment (Ticagrelor: 57%, Prasugrel: 47%, P<.01) and 7 percentage‐points more likely to switch medication (Ticagrelor: 35%, Prasugrel: 28%, P<.01). After adjusting for multiple factors, including time‐varying exposure and censoring imbalance, ticagrelor was associated with a higher risk of all‐cause death, MI, or stroke when compared to prasugrel (Hazard ratio (HR): 1.33; 95% CI: 1.04‐1.68). Similarly, ticagrelor was associated with a higher risk in bleeding events when compared with prasugrel (HR: 1.61; 95% CI: 1.19‐2.17).
Conclusion: When compared with ticagrelor, prasugrel use following PCI for ACS was associated with a lower risk of death, MI, or stroke, as well as a reduced risk of major bleeding.
Belviso, N., Aronow, H.D., Wyss, R., Barbour, M., Zhang, Y., Wen, X. and Kogut, S. (2021), Comparative Effectiveness and Safety of Prasugrel versus Ticagrelor following Percutaneous Coronary Intervention: An Observational Study. Pharmacotherapy. Accepted Author Manuscript. https://doi.org/10.1002/phar.2530
Available at: https://doi.org/10.1002/phar.2530