Assessment of Cardiovascular Events Caused by New-Generation Androgen Receptor Pathway Inhibitors Used for Prostate Cancer: A Real-World Study in Japan

Introduction: Androgen receptor pathway inhibitors (ARPIs) that significantly improve the prognosis of patients with prostate cancer include abiraterone acetate (androgen synthesis inhibitor) and enzalutamide (androgen receptor inhibitor). A recent analysis of ARPI and cardiovascular events using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) has been reported; however, the evidence on cardiovascular events for abiraterone acetate and enzalutamide in real-world clinical practice is insufficient. Using a large Japanese database of medical institutions, the Japanese Medical Data Center (JMDC) medical institution database (JMDC Inc., Tokyo, Japan), this study tested the hypothesis that the risk of cardiovascular events with enzalutamide is lower than that with abiraterone acetate. Method: Using the JMDC medical institution database, patients with new use of abiraterone acetate or enzalutamide who had not experienced a major cardiovascular event between October 2014 and February 2022 were included. After adjusting for age, comorbidities, and concomitant medications using propensity score matching, cumulative incidence rates were compared for cardiovascular death and all cardiovascular events as the primary endpoints, and major cardiovascular events, myocardial infarction, heart failure, and stroke as secondary endpoints. Result: A total of 3,033 patients in the enzalutamide group and 2,021 in the abiraterone group met the eligibility criteria. After propensity score matching, the cohort included 1,940 patients in the enzalutamide group and 1,940 patients in the abiraterone group. Enzalutamide was associated with significantly lower cumulative rates of cardiovascular death (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.10-0.93), all cardiovascular events (HR: 0.79, 95% CI: 0.64-0.98), major cardiovascular events (HR: 0.79, 95% CI: 0.64-0.97), and myocardial infarction (HR: 0.62, 95% CI: 0.46-0.84) compared to abiraterone. Conclusion: In a national sample of males with prostate cancer, those newly treated with enzalutamide had a lower risk of adverse cardiovascular events than those treated with abiraterone acetate.