Abstract Body (Do not enter title and authors here): Introduction: Prostate cancer (PCa) is the most common cancer in men. Androgen deprivation therapy (ADT) is the primary systemic therapy for PCa, with over 500,000 men in the US being treated with ADT each year. Despite the most widely utilized form of ADT––gonadotropin-releasing hormone (GnRH)-agonists, such as leuprolide––being associated with accelerated coronary atherosclerosis and an increased risk of cardiovascular mortality, strategies to mitigate GnRH-agonist ADT-associated coronary atherosclerosis remain undefined.

Research Question: Whether baseline statin use at the time of ADT initiation mitigates GnRH-agonist ADT-associated coronary atherosclerosis progression is unknown.

Methods: This study included men with localized PCa and without coronary heart disease recruited to the REVELUTION clinical trial (NCT05320406) between 6/2022 and 3/2024. According to cancer risk, participants were treated with prostate radiation therapy (RT) alone without ADT or randomized to either RT with GnRH-agonist leuprolide or GnRH-antagonist relugolix for ≥ 6 months. The primary endpoint was change in coronary total plaque volume (ΔTPV) on CCTA from baseline to 12 months following treatment initiation. Comparisons between treatments arms were assessed according to baseline statin use with analysis of covariance and adjusted for age and baseline TPV.

Results: Of 94 eligible participants, 90 (N=28, RT without ADT; N=31, RT with leuprolide; N=31, RT with relugolix) were enrolled. Mean age was 67.5 (SD 8.1) years, 26% (N=23) were Black, and 56% (N=50) were on a statin at baseline. Among leuprolide-treated participants, median 1-year ΔTPV was +101.0 [IQR 53.5-272.5] mm³ in statin non-users and +35.0 [IQR 5.3-82.0] mm³ in statin users (P=0.03). When compared to the no ADT arm, leuprolide treatment in statin non-users was associated with significantly increased mean-adjusted 1-year ΔTPV (+117.9 mm³, 95% CI 53.3-182.4, P<0.001) versus statin users (+4.9 mm³, 95% CI -53.7-63.5, P=0.87, P-interaction=0.002). Baseline statin use did not modify the relationship between relugolix versus no ADT and ΔTPV (P-interaction=0.25).

Conclusions: Concurrent statin therapy at the time of leuprolide initiation for PCa was significantly associated with decreased coronary atherosclerosis progression when compared to those not on statins at baseline. Future prospective study should analyze the impact of concurrently initiated statin therapy on leuprolide-associated coronary atherosclerosis.