Top Line: Why does relugolix carry less cardiac risk than leuprolide despite no detriment in testosterone suppression?
The Study: In the REVELUTION trial 62 men with localized prostate cancer receiving radiation plus at least 6 months of ADT were assigned to oral relugolix or leuprolide with serial coronary CT angiography with AI-enabled quantitative plaque analysis. At 12 months, leuprolide versus relugolix was associated with a significantly greater increase in total plaque volume and noncalcified plaque volume–two imaging biomarkers known to portend subsequent major adverse cardiovascular events. As expected, testosterone suppression was comparable between arms, further implicating divergence in pathways not potencies. These imaging findings provide a plausible mechanistic underpinning for the significant reduction in major cardiac events seen with relugolix versus leuprolide in the HERO trial: accelerated, predominantly noncalcified plaque progression.
TBL: This small trial is the first to identify biologic mechanisms underlying the accentuated cardiovascular risk observed with GnRH-agonists versus -antagonists, namely accelerated coronary atherosclerosis. | Patel, JAMA Cardiol 2026
The Study: In the REVELUTION trial 62 men with localized prostate cancer receiving radiation plus at least 6 months of ADT were assigned to oral relugolix or leuprolide with serial coronary CT angiography with AI-enabled quantitative plaque analysis. At 12 months, leuprolide versus relugolix was associated with a significantly greater increase in total plaque volume and noncalcified plaque volume–two imaging biomarkers known to portend subsequent major adverse cardiovascular events. As expected, testosterone suppression was comparable between arms, further implicating divergence in pathways not potencies. These imaging findings provide a plausible mechanistic underpinning for the significant reduction in major cardiac events seen with relugolix versus leuprolide in the HERO trial: accelerated, predominantly noncalcified plaque progression.
TBL: This small trial is the first to identify biologic mechanisms underlying the accentuated cardiovascular risk observed with GnRH-agonists versus -antagonists, namely accelerated coronary atherosclerosis. | Patel, JAMA Cardiol 2026