INTRODUCTION: Recent real-world studies compared effectiveness and safety of enzalutamide (ENZA) and abiraterone acetate (AA) for metastatic castration-resistant prostate cancer (mCRPC). The growing evidence needs further substantiation with long-term data. This study, the first to use German data, investigated cardiovascular (CV) event risk and overall survival (OS) in patients initiating ENZA or AA. AA (2012) and ENZA (2014) are widely used for mCRPC in Germany. METHODS: This retrospective study used data of chemotherapy-naïve patients with mCRPC on ENZA or AA (2012-2020) from two German claims databases (AOK PLUS and GWQ ServicePlus). The primary endpoint was time to first CV event (CV-related hospitalization) analyzed via a meta-analysis of Cox proportional hazard models of propensity score-matched (PSM) intention-to-treat cohorts. Other endpoints were baseline characteristics, CV event rate, number of CV events per patient, and OS. RESULTS: Of 2240 patients in the total study population (ENZA, 828
AA, 1412), 796 PSM patients were included in each group. ENZA patients were older and had a higher prevalence of some comorbidities, but without meaningful differences after PSM. Further, 386 patients had ≥ 1 CV event (ENZA, 172
AA, 214). ENZA was associated with a significantly lower risk of CV events (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.57-0.86, p = 0.002, I CONCLUSIONS: The unmatched ENZA cohort had higher average age and more comorbidities than the AA cohort, but no meaningful differences were noted after PSM. ENZA was associated with a significantly lower risk of CV events and improved OS.