Cardiovascular Risk With Androgen-Deprivation Therapy for Prostate Cancer

Zosia Chustecka

February 01, 2010

February 1, 2010 — "There may be a relationship" between androgen-deprivation therapy (ADT) for prostate cancer and cardiovascular risk, states a new advisory issued jointly by the American Heart Association (AHA), the American Cancer Society, and the American Urological Association.

ADT is a mainstay of treatment for prostate cancer, the group explains, and it has been shown to extend survival in certain patient populations. Although there have been several studies suggesting that patients receiving ADT have an increased risk for cardiovascular disease and mortality, other studies have not shown any such association.

A causal relation between ADT and cardiovascular events "cannot be determined definitely at this point," the advisory states. "However, it is plausible," the authors add.

The advisory was published online on February 1 in Circulation.

Its purpose is "strictly informative," the authors explain. "This advisory should not be construed as dictating clinical practice or superseding the clinical judgment of physicians, and it should not be used for medicolegal purposes," they emphasize.

Nonetheless, there are a few recommendations. The writing group, which includes cardiologists, urologists, and oncologists, says that it reached a consensus on the following points:

  • For patients in whom ADT is believed to be beneficial, there is no clear indication that they be referred for evaluation by internists, endocrinologists, or cardiologists prior to initiating ADT, or that they undergo specific cardiac testing.

  • The decision of whether or not to initiate ADT in patients with cardiac disease, in whom the benefits of therapy would be weighed against any possible risks, is most appropriately made by the physician treating the patient for prostate cancer.

  • Patients receiving ADT should be referred to their primary care physician for periodic follow-up evaluation of the potential metabolic effects of ADT.

  • Patients with cardiac disease should receive secondary preventative measures, as recommended by the AHA, including, when appropriate, lipid-lowering therapy, antihypertensives, glucose-lowering therapy, and antiplatelet therapy.

ADT usually consists of treatment with a gonadotropin-releasing hormone (GnRH) agonist, such as leuprolide, goserelin, and triptorelin, although antiandrogens, such as flutamide and bicalutamide, are often used as well, in combination with the GnRH agonists.

Prompted by Several New Studies

The advisory was prompted by several new studies that reported an increase in cardiovascular events, including an increase in myocardial infarction and cardiovascular death, in prostate cancer patients who were being treated with ADT (Keating NL et al. J Clin Oncol. 2006;24:4448-4456; Saigal CS et al. Cancer.2007;110:1493-1500; D'Amico AV et al. J Clin Oncol. 2007;25:2420-2425; Tsai HK et al. J Natl Cancer Inst 2007; 99:1516-1524; D'Amico Av et al. Cancer. 2008;113:3290-3297).

Most likely as a result of these reports, there has been an increase in internists, endocrinologists, and cardiologists being consulted about patients receiving ADT, the working group notes, adding that many of these physicians have been unaware of the potential problem.

"This advisory aims to fill that information gap and make some informed statements synthesizing the data to help guide clinicians as they treat patients," said lead author and chair of the working group, Glenn Levine MD, FAHA, professor of medicine at Baylor College of Medicine in Houston, Texas.

"There are fairly good data that ADT impacts cardiovascular risk factors. There are data suggesting that ADT increases cardiovascular risk, although at this time the data cannot be considered to be definitive," he said in an interview with Medscape Oncology. "We believe that physicians should be aware of it."

Currently, cardiologists do not need to be directly involved in the evaluation of patients for ADT prior to the initiation of ADT, said Dr. Levine, a cardiologist himself. "The physician prescribing the ADT, whether an oncologist, urologist, or radiation oncologist, does not need to feel obligated to refer every patient for cardiology evaluation before initiating ADT; it is the prescribing physician that is best placed to weigh the benefits of ADT against any potential side effects," he said.

If patients receiving ADT are referred to a cardiologist, there are currently no data to suggest that the cardiologist feel obligated to carry out a stress test, catheterization, or stent placement for revascularization, Dr. Levine added.

However, because ADT does seem, in many people, to have an impact on cardiovascular risk factors, patients should be referred to their primary care physicians for monitoring, and their primary care physicians should be made aware of the fact that the patient is receiving ADT, Dr. Levine continued. This should ensure optimal preventive care, such as controlling lipids and blood pressure, and more general advice to not smoking, not be overweight, and to exercise regularly. This is true for primary prevention in patients who have not had a cardiovascular event and for secondary prevention in patients after an event, he said.

Mechanisms Involved Are Unclear

The mechanism by which ADT might increase cardiovascular risk, if indeed it does, is unclear. In the paper, the authors note that ADT has metabolic effects that can include increasing body weight, reducing insulin sensitivity, and/or increasing serum cholesterol and triglyceride levels. They also point out that the pattern of metabolic alteration appears to be distinct from the classically defined metabolic syndrome.

However, whether it is these effects or some other mechanisms that are involved remains to be determined, Dr. Levine said. It might be that there are multifactorial effects, he continued, with different mechanisms involved in different patients.

Most of the 18 authors in the working group have disclosed no relevant financial relationships, but 3 report serving as consultants or advisory board members for various pharmaceutical companies, as detailed in the paper.

Circulation. Published online February 1, 2010.

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