In men with localized prostate cancer (PCa) treated with radiation and androgen-deprivation therapy (ADT), treatment with the gonadotropin-releasing hormone (GnRH) leuprolide was associated with a significant 12-month increase in coronary artery plaque volume when compared with treatment with relugolix, according to a brief report of the REVELUTION trial published Feb. 18 in JAMA.

This open-label, randomized trial was conducted at four centers affiliated with a single academic institution in Atlanta, GA. Participants included 62 men (mean age of 69 years, 56% taking statins) with nonmetastatic PCa without prior ADT exposure who were receiving pelvic radiotherapy with ADT for six months or longer. Trial enrollment was completed from June 16, 2022, through March 6, 2024, and patients were assigned 1:1 to leuprolide acetate (22.5 mg injection every three months) or relugolix (120 mg once daily after a single loading dose of 360 mg). Data analysis took place from March 31, 2025, through June 23, 2025.

The primary endpoint was the change in coronary artery total plaque volume (TPV), measured by coronary CT angiography at baseline and 12 months after ADT initiation. The secondary endpoint was the change in coronary artery noncalcified plaque volume (NCPV). Change in calcified plaque volume (CPV) and low-attenuation plaque volume (LAPV) were also measured.

Results at 12 months showed that compared with relugolix, there was a significantly greater increase in TPV (estimated difference +68.9 mm³; p=0.02) and NCPV (+64.5 mm³; p=0.004) after adjustment for baseline age, plaque volume and statin use. The 12-month changes in CPV and LAPV were not significantly different between the two groups.

In what they believe is the “first clinical trial to identify a biological basis for [cardiovascular] risk differences observed between ADT drug pathways in men with PCa,” Sagar A. Patel, MD, MSc, et al., write their results “support the hypothesis that [cardiovascular] risk from ADT may be driven by accelerated coronary atherosclerosis, which is more prominent with GnRH agonist therapy.”