Researchers in Italy recently reviewed 48 clinical trials and meta-analyses, published since 2010, which examined the link between ADT and cardiovascular disease. Both retrospective observational studies as well as randomized controlled trials (RCTs) were included in the review. This amounted to data on tens of thousands of patients, so you would think that the authors would have arrived as some clear and precise answers. But they didn’t. The problem was that the different studies used different methodologies and disparate definitions of cardiovascular diseases/toxicities.
So what did the authors find?
Depending in part on the drugs used, ADT is associated with:
Increased risk of metabolic syndrome, which involves increases in fat mass, decreases in muscle mass, dyslipidemia, hyperglycemia, insulin resistance, and hypertension. Metabolic syndrome can lead to diabetes and a number of cardiovascular complications.
Elevations in levels of inflammatory molecules, which may contribute to the formation of atherosclerotic plaque in the blood vessels. This can increase the risk of cardiovascular accidents, peripheral artery disease, and blood clots.
Impacts on cardiac ion channels that regulate heart rhythms, which may increase the risk of heart attacks.
The risks overall appear somewhat lower in RCTs, but this may be because RCTs often exclude patients who already have high cardiovascular risk. Furthermore, it’s often difficult to control for other factors that might influence study results, including other medications the patients may be taking, different rates of treatment adherence, and other underlying health conditions.
There are two main takeaways from this systematic review:
Cardiovascular diseases remain the most common co-morbidity and cause of death for men with prostate cancer. As such, the authors state that “a careful [cardiovascular] assessment is essential in all prostate cancer patients undergoing hormone therapy.”
More prospective studies and randomized controlled trials to specifically assess cardiovascular toxicities are needed. Further, evidence-based guidelines for optimal ADT use are needed, particularly for patients at increased risk of cardiovascular diseases.
To read the study abstract, see: https://pubmed.ncbi.nlm.nih.gov/32500365/
Cereda, V., Falbo, P.T., Manna, G., Iannace, A., Menghi, A., Corona, M., Semenova, D., Calo, L., Carnevale, R., Frati, G., & Lanzetta, G. (2020). Hormonal Prostate Cancer Therapies and Cardiovascular Disease: A Systematic Review. Heart Failure Reviews. Epub ahead of print.