REVELUTION Trial: GnRH Antagonists Show Less Coronary Plaque Progression Than Agonists in Prostate Cancer ADT

Relugolix showed less coronary plaque progression than leuprolide in men receiving androgen deprivation therapy with prostate cancer and pelvic radiotherapy, according to the REVELUTION trial. The prospective study enrolled 94 ADT-naïve men from June 2022 to March 2024, with 90 completing analysis across three arms: radiotherapy alone (n=28), radiotherapy plus leuprolide (n=31), and radiotherapy plus relugolix (n=31). Coronary CT angiography measured total plaque volume (TPV) change at 12 months as the primary endpoint, with non-calcified plaque volume (NCPV) and major adverse cardiovascular events (MACE) as secondary outcomes.

Leupolide increased median TPV by 52.0 mm³ (IQR 19.5-159.0), compared to 25.0 mm³ (-6.0-46.0) with relugolix and 13.0 mm³ (-19.0-45.0) without ADT (P=0.02 between leuprolide and relugolix).
After adjustment for baseline plaque, age, and statin use, leuprolide differed from control by +79.1 mm³ (P=0.004) while relugolix showed +10.5 mm³ (P=0.69). NCPV followed a similar pattern, with leuprolide at +71.9 mm³ versus control (P=0.001) and relugolix at +7.2 mm³ (P=0.73).

Over median 2.2-year follow-up, MACE occurred in 3/31 (9.7%) on leuprolide, 0/31 on relugolix, and 1/28 (3.6%) without ADT. The trial, funded by the Prostate Cancer Foundation, suggests GnRH agonists accelerate atherosclerosis more than antagonists despite equivalent testosterone suppression.

Source.

Clinical trial.