Thromboembolic Events in Castration‐Resistant Prostate Cancer Patients With and Without Cardiovascular Comorbidities Receiving Oral Androgen Receptor Pathway Inhibitors

BACKGROUND: This study investigates the association between thromboembolic events (TE) and castration-resistant prostate cancer (CRPC) patients receiving oral androgen receptor pathway inhibitors (ARPi) compared to those undergoing chemotherapy, both with and without a pre-existing history of cardiovascular disease (CVD). METHODS: A total of 2779 men diagnosed with CRPC were identified using the Surveillance, Epidemiology, and End Results (SEER) Medicare Linked Database from 2012 to 2016. Patients were stratified based on their CVD history. Within each CVD stratum (pre-existing CVD vs. no pre-existing CVD), patients were further categorized into two treatment groups: those receiving oral ARPi and those undergoing chemotherapy. Unadjusted and inverse probability treatment weight (IPTW)-adjusted proportional hazards models, using Fine and Gray's method, were applied to evaluate the potential association between ARPi treatment and TE. RESULTS: Patients with pre-existing CVD treated with ARPi exhibited a significantly lower crude hazard ratio (HR) for TE compared to chemotherapy (HR 0.39, 95% CI 0.27-0.58, p < 0.001). However, after adjustment using IPTW, this association was no longer significant (adjusted hazard ratio [AHR] 1.00, 95% CI 0.75-1.32, p = 0.99). For patients without CVD, ARPi use was also associated with a reduced risk of TE in the crude analysis (HR 0.53, 95% CI 0.32-0.87, p = 0.01), but this effect was not statistically significant after IPTW adjustment (HR 0.99, 95% CI 0.69-1.41, p = 0.94). CONCLUSION: ARPi demonstrated no significant effect on TE risk compared to chemotherapy, regardless of pre-existing CVD status. Similarly, when excluding patients with a prior history of TE, ARPi use remained non-significantly associated with new TE in the IPTW-adjusted competing risk analysis, highlighting the need for further investigation.