Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a prospective cohort study

Abstract Background While the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients.Methods Adult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this prospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone use without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 31 September 2021. The primary outcome was MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups.Results In total, 1015 patients were analyzed (559 enzalutamide users and 456 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3–21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59–0.86], p < 0.001), which remained consistent in multivariable analysis (p < 0.001). Such an association may be stronger in patients aged ≥ 65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI 0.33–0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI 0.59–0.85], p < 0.001).Conclusion Enzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients.