Several studies have suggested that men who receive androgen-deprivation therapy (ADT) to treat prostate cancer may face an increased risk of dying from cardiovascular causes. But a new analysis of clinical trial results has found no evidence that ADT increases cardiovascular deaths among men with high-risk, nonmetastatic prostate cancer.
The findings, from a meta-analysis of eight randomized clinical trials, appeared in the December 7 issue of JAMA. Androgen-deprivation therapy, which suppresses the production of male hormones, is a mainstay of prostate cancer care. A form of ADT known as gonadotropin-releasing hormone agonist therapy has been linked to heart disease in some, but not all, studies.
Citing these studies, the Food and Drug Administration last year issued a safety warning for this class of drugs. Several medical societies have also issued a science advisory stating that there may be a relationship between ADT and cardiovascular events and death.
To explore this question further, Dr. Paul Nguyen of Dana-Farber Cancer Institute and his colleagues analyzed data on more than 4,000 participants in ADT trials. Among 2,200 men treated with ADT, there were 255 cardiovascular deaths (an overall incidence rate of 11.0 percent); among 1,941 men in the control groups, there were 252 deaths (11.2 percent).
The study also showed a benefit: Men who received ADT had a lower risk of dying from prostate cancer and other causes of death than men who did not. “Our study should be reassuring to most men with high-risk prostate cancer considering ADT,” noted Dr. Nguyen.
The main caveat of the study is that the researchers could not assess the risk of cardiac death for specific subgroups of patients, including those at highest risk for cardiovascular disease. Therefore, Dr. Nguyen said, “our study could not rule out the possibility that men with a history of cardiac disease could still be harmed by ADT.”
For men with significant underlying cardiac disease, the study authors recommend a careful examination by a cardiologist and a discussion of the risks and benefits of ADT.
Although ADT is not new, doctors are still learning about its risks and benefits, noted the authors of an accompanying editorial. Some research, for example, has suggested that ADT may shorten the time before a cardiovascular event occurs. (The current study could not address this question.)
To answer such questions, future prospective trials involving ADT should classify patients according to cardiovascular risk factors at the beginning of a study, noted the study’s senior author, Dr. Toni Choueiri of Dana-Farber Cancer Institute.
“While it is important to raise awareness of the possible cardiac side effects of ADT, it may be the case that the pendulum had swung too far away from the use of ADT, even for men with high-risk disease in whom ADT has been shown to save lives,” Dr. Choueiri wrote in an e-mail.