Faculty of Medicine, Department of Urology, McGill University Montreal, Quebec, Canada
Background: Novel hormonal agents (NHAs) such abiraterone acetate (ABI) and enzalutamide (ENZ) are two oral drugs that 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.
Objectives: 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. Patients were selected on the basis of having initiated a novel hormonal agent (ABI or ENZ) between 2011 and 2016. 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. Weighted Cox proportional hazards regression was then used to estimate the association between NHA group and study outcomes.
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. After applying IPTW, all baseline variables were well balanced across both groups with absolute standardized differences < 10%. 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 hospitalization 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.