Dr. Weeks’ Comment: Too many of my patients on androgen deprivation therapy (ADT) to lower testosterone suffer from heart disease which is not surprising since the heart if a muscle and lower testosterone levels create less muscle mass. There are better ways to reduce prostate cancer risk without compromising your most important muscle: your heart.
Which Type of Prostate Cancer ADT Is Safer for the Heart?
Edited by Amy Norton
TOPLINE:
In a small, randomized trial, men on androgen deprivation therapy (ADT) for localized prostate cancer had significantly faster progression of coronary artery disease when treated with leuprolide vs relugolix.
METHODOLOGY:
- ADT with injectable gonadotropin-releasing hormone (GnRH) receptor agonists such as leuprolide has been associated with cardiovascular morbidity, and cardiovascular disease is the leading cause of death in men with prostate cancer. The oral GnRH antagonist relugolix was shown to carry lower cardiovascular risks than leuprolide in the HERO trial, but the reasons remain unclear.
- To investigate, researchers conducted an open-label randomized clinical trial, enrolling 65 men with nonmetastatic prostate cancer receiving pelvic radiotherapy plus at least 6 months of ADT. Patients were randomly assigned 1:1 to receive either leuprolide (22.5 mg by injection every 3 months) or relugolix (120 mg orally once daily, after a single loading dose of 360 mg).
- The primary endpoint was 12-month change in coronary artery total plaque volume, measured by coronary computed tomographic angiography. The secondary endpoint was change in noncalcified plaque volume.
TAKEAWAY:
- Overall, total plaque volume increased in both ADT groups, but significantly more so in men taking leuprolide. Compared with relugolix, treatment with leuprolide was associated with a greater 12-month increase in total plaque volume (estimated difference, +68.9 mm3; P = .02), after adjustment for baseline plaque volume, age, and statin use.
- The faster progression with leuprolide was driven by changes in noncalcified plaque volume, specifically. Noncalcified plaques tend to be less stable and are strongly associated with heart attack and other major cardiovascular events, the authors noted.
- Patients’ testosterone levels declined at month 3 and 6, with no significant differences between the leuprolide and relugolix groups, suggesting the cardiovascular effect of ADT may be unrelated to the magnitude of testosterone suppression.
IN PRACTICE:
“Our data demonstrate that the [cardiovascular] effect of ADT is detectable in the near term, at least partly mediated by coronary artery plaque progression, and is drug pathway-specific independent of testosterone suppression,” the study authors wrote. They noted that, to their knowledge, this is the first study to identify a biological basis for the differing cardiovascular risks that have been observed with different ADT types.
SOURCE:
The study, led by Sagar A. Patel, MD, of Emory University in Atlanta, was published in JAMA Cardiology.
LIMITATIONS:
Most patients in this cohort had coronary disease at baseline, which may limit generalizability to healthier populations. Changes in statin dose after baseline were not recorded, which could have influenced plaque progression. The study was powered to detect differences in plaque volumes but was not large enough to measure the impact of leuprolide vs relugolix on clinical cardiovascular outcomes.
DISCLOSURES:
The trial received support from the Prostate Cancer Foundation, Pfizer, and Sumitomo Pharma Switzerland GmbH. Several co-authors disclosed financial relationships with Pfizer, Sumitomo, or other commercial sources. Additional disclosures are noted in the original article.