Late last month, two papers were published within a day of each other discussing the risk of cardiovascular disease (CVD) for patients on ADT. They both had many prestigious coauthors and were published in high impact journals. One of the journals was Cancer. The other was Circulation: genomics and precision medicine and was an official statement from the American Heart Association (AHA).
Note what we have bolded in the following two paragraphs…
The AHA review stated that “patients with prostate cancer and baseline CVD and cardiovascular risk factors experience increased rates of cardiovascular events when treated with androgen deprivation therapy.“ The statement then continued with: “prolonged use of some hormonal therapies worsens cardiovascular risk factors and metabolic syndrome…“
The paper published in Cancer was a bit narrower in its focus and looked at patients who received radiotherapy (RT) for prostate cancer with or without adjuvant ADT. There the authors concluded that “the use of ADT with RT, compared with RT alone, is not associated with an increased risk of cardiovascular-specific mortality, even among sub groups of men with pre-existing comorbidities, including cardiovascular disease.“
These conclusions are almost completely opposite to each other. How is this possible?
The paper suggesting little or no cardiovascular risk was a retrospective analysis of data collected on 1463 men between 1993 and 2001. The other paper was a comprehensive review of all the studies published to date. It explored the impact of different drug treatments, many of which were not available before 2001. The AHA paper reviewed possible mechanisms to account for how ADT could increase cardiovascular risk based on data from the different drugs.
We cannot be sure why the study in Cancer found no impact of ADT on CVD risk, but there are a couple of reasons why this may be the case. First, the data were collected a long time ago when more men were smoking. Today, with fewer men smoking and with newer drug treatments available, men starting on ADT are likely to live longer; therefore, the risk of death from causes other than prostate cancer is higher. Second, the study in Cancer only followed the men for five years. Now many men on ADT live much longer than that. The study’s conclusions may not reflect the long term CVD risks for men now starting on ADT.
Given the commonality of CVD we still need to be concerned about the risk of cardiovascular disease for men on ADT.
Both papers acknowledge that the data are not consistent across all studies and that more research is necessary to sort out the long-term impact of ADT on CVD. Both papers also recognize the serious risk of metabolic syndrome for men on ADT long term. Both note the importance of men making lifestyle adjustments to reduce the chances of developing metabolic syndrome, which can lead not only to CVD but also to diabetes. Both papers agree on that point.
To read the Cancer study abstract, see: https://pubmed.ncbi.nlm.nih.gov/33905530/
To read the AHA study abstract, see: https://pubmed.ncbi.nlm.nih.gov/33896190/
References:
Butler SS, Mahal BA, Moslehi JJ, Nohria A, Dee EC, Makkar R, Whitbeck A, Wangoe J, Mouw KW, Nguyen PL, Muralidhar V. Risk of cardiovascular mortality with androgen deprivation therapy in prostate cancer: A secondary analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Randomized Controlled Trial. Cancer. 2021 Apr 27. doi: 10.1002/cncr.33486. Epub ahead of print. PMID: 33905530.
Okwuosa TM, Morgans A, Rhee JW, Reding KW, Maliski S, Plana JC, Volgman AS, Moseley KF, Porter CB, Ismail-Khan R; American Heart Association Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Cardiovascular Radiology and Intervention. Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association. Circ Genom Precis Med. 2021 Apr 26:HCG0000000000000082. doi: 10.1161/HCG.0000000000000082. Epub ahead of print. PMID: 33896190.