Comparative Cardiovascular Safety of Novel Hormonal Agents in Metastatic Castration-Resistant Prostate Cancer Using Real-World Data

Abstract

Background: Novel hormonal agents (NHAs) such as abiraterone acetate (ABI) and enzalutamide (ENZ) are frequently used in metastatic castration-resistant prostate cancer (mCRPC). Despite their overall tolerable risk profile, certain signals of cardiovascular toxicity were reported for these agents in clinical trials but little is known about their incidence in clinical practice. The objective was to assess the comparative cardiovascular safety of ABI and ENZ in patients with mCRPC in the real-world.

Methods: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. First-time NHA users between 2011 and 2016 were selected. The primary outcome of interest was cardiovascular-related hospitalization (composite outcome that included acute coronary syndrome, cerebrovascular stroke, heart failure, arrhythmia and others). Inverse probability of treatment weighting (IPTW) with the propensity score was used to adjust for measured baseline characteristics including pre-existing cardiovascular disease.

Results: The cohort comprises 2,183 patients, with 1,773 (81.2%) in the ABI group and 410 (18.8%) in the ENZ group. Crude incidence rates of cardiovascular-related hospitalization were of 9.8 events per 100 person-years (PYs) and of 7.1 events per 100 PYs for the ABI and ENZ groups, respectively. The ABI group was at greater risk of cardiovascular-related hospitalization compared to the ENZ group (IPTW-hazard ratio (HR) 1.82; 95% confidence interval (95%CI) 1.09-3.05). The risk of hospitalization for heart failure was greater in ABI (IPTW-HR 2.88; 95%CI 1.09-7.63).

Conclusions: Our findings suggest that ABI users may be at greater risk of cardiovascular-related hospitalization compared to ENZ users, in particular for heart failure. These results provide clinicians with additional insight on the cardiovascular risks of mCRPC patients treated with NHAs in the real-world and further large studies are required to corroborate these findings.

Keywords: Abiraterone; Adverse Events; Cardiotoxicity; Enzalutamide; Real-World Evidence.