Leuprolide Drives Significantly Higher Coronary Plaque Growth vs Relugolix in Patients With Prostate Cancer
Key Clinical Takeaways
- Design/Population: The REVELUTION trial prospectively evaluated 90 patients with localized prostate cancer treated with radiotherapy alone or radiotherapy plus ADT randomized to leuprolide or relugolix. Coronary CT angiography was obtained at baseline and 12 months to quantify plaque progression, with TPV as the primary end point.
- Key Outcomes: Leuprolide caused significantly greater increases in total, noncalcified, calcified, and low-attenuation plaque volumes compared with relugolix or RT alone. MACE occurred more frequently with leuprolide, while relugolix showed no significant plaque progression and no cardiovascular events.
- Clinical Relevance: These findings provide mechanistic evidence that GnRH agonists may accelerate coronary atherosclerosis more than GnRH antagonists. Relugolix may represent a safer ADT option for patients with prostate cancer who are at increased cardiovascular risk.
Updated results from the REVELUTION trial show that androgen deprivation therapy (ADT) with leuprolide leads to significantly greater coronary plaque progression than relugolix among patients with prostate cancer.
These results were presented by Sagar Patel, MD, Emory University, Decatur, Georgia, at the 2025 American Heart Association Resuscitation Science Symposium in Chicago, Illinois.
In this open-label trial, 94 treatment-naïve patients received pelvic radiotherapy alone (n = 28) or in combination with either leuprolide (n = 31) or relugolix (n = 31) for at least 6 months. Coronary computed tomography angiography was performed at baseline and 12 months after treatment initiation. The primary end point was change in total coronary artery plaque volume. Key secondary end points included changes in noncalcified plaque volume, calcified plaque volume, low-attenuation plaque volume, and incidence of major cardiovascular events.
At analysis, the median change in total coronary artery plaque volume was +13 mm³ in the radiotherapy arm, +52 mm³ in the leuprolide arm, and +25 mm³ in the relugolix arm (P = .02). Major cardiovascular events occurred in 1 patient in the radiotherapy arm, 3 patients in the leuprolide arm, and no patients in the relugolix arm.
Compared with radiotherapy alone, leuprolide was associated with significantly greater increases in total plaque volume (+79.1 mm³; P = .004), noncalcified plaque volume (+71.9 mm³; P = .001), calcified plaque volume (+19.9 mm³; P = .04), and low-attenuation plaque volume (+5.1 mm³; P = .03). In contrast, relugolix did not significantly increase total plaque volume (+10.5 mm³; P = .69), noncalcified plaque volume (+7.2 mm³; P = .73), calcified plaque volume (+8.9 mm³; P = .34), or low-attenuation plaque volume (+1.3 mm³; P = .56).
As Dr Patel concluded, “ADT for [prostate cancer] is associated with accelerated coronary atherosclerosis within 12 months and is significantly higher with GnRH-agonist leuprolide compared with GnRH-antagonist relugolix.”
Source:
Patel S, Yadalam A, Van Assen M, et al. Accelerated coronary atherosclerosis following relugolix versus leuprolide androgen deprivation therapy in men with prostate cancer (REVELUTION): An open-label randomized controlled trial. Presented at the 2025 American Heart Association's Resuscitation Science Symposium. November 7 - 8, 2025. Chicago, Illinois. Abstract 4352126
