ADT and CV risk: Two studies offer new insights

Two recently published studies provide new insight on cardiovascular morbidity and mortality associated with androgen deprivation therapy (ADT) in men with prostate cancer.

One study found that ADT is linked with an increased risk of dying from cardiovascular-related causes only in men with congestive heart failure or prior myocardial infarction. The authors of a second study reported that the risk of cardiac events is significantly lower among men treated with a gonadotropin-releasing hormone (GnRH) antagonist compared with GnRH agonists.

RELATED: ADT overuse remains a problem among some urologists

In the first paper, researchers from the Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School in Boston analyzed data on 5,077 men with prostate cancer who were treated between 1997 and 2006. Thirty percent of these men received ADT, while the others did not.

After a median follow-up of 4.8 years, no association was detected between ADT and heart-related deaths in men with no cardiac risk factors (1.08% at 5 years for ADT vs. 1.27% at 5 years for no ADT) or in men with diabetes, hypertension, or high cholesterol (2.09% vs 1.97%). However, ADT was associated with a 3.3 times increased risk of cardiac-related deaths in men with congestive heart failure or prior heart attacks. In this subgroup, heart-related deaths occurred in 7.01% of men receiving ADT versus 2.01% of men not receiving it after 5 years, reported senior author Paul Nguyen, MD, of Dana-Farber/Brigham and Women's Cancer Center.

This suggests that administering the therapy to 20 men in this potentially vulnerable subgroup could result in one cardiac death, Dr. Nguyen, first author David Ziehr of Harvard Medical School, and colleagues said in a press release. 

Study findings were published online in BJU International (Oct. 29, 2014).

"While androgen deprivation therapy can be a lifesaving drug for men with prostate cancer and significantly increase the cure rates when used with radiation for aggressive disease, this study also raises the possibility that a small subgroup of men who have significant heart disease could experience increased cardiac death on ADT," Dr. Nguyen said.

He noted that because the study was retrospective, it must be carefully weighed against larger controlled trials that have demonstrated the benefits of ADT.

"I would still say that for men with significant heart problems, we should try to avoid ADT when it is not necessary-such as for men with low-risk disease or men receiving ADT only to shrink the prostate prior to radiation. However, for men with high-risk disease, in whom the prostate cancer benefits of ADT likely outweigh any potential cardiac harms, ADT should be given even if they have heart problems, but the patient should be followed closely by a cardiologist to ensure that he is being carefully watched and optimized from a cardiac perspective."

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The second study, a pooled data analysis, was designed to determine whether cardiovascular morbidity differs following initiation of GnRH agonists (leuprolide or goserelin) versus a GnRH antagonist (degarelix [Firmagon]).

Researchers examined pooled data from six phase III prospective randomized trials that recruited more than 2,000 men to compare the efficacy of GnRH agonists versus an antagonist. Recruited men had pathologically confirmed prostate cancer, an Eastern Cooperative Oncology Group score <2, a minimum life expectancy of 1 year, and were naïve to ADT.

Men were excluded if they had risk factors for heart failure, hypokalemia, or a family history of long QT syndrome, or had another cancer diagnosed within 5 years. Men were randomized to receive a GnRH agonist or degarelix for either 3 to 7 months or 12 months. The two groups had common baseline characteristics.

“Among men with preexisting cardiovascular disease, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men treated with a GnRH antagonist compared with GnRH agonists (hazard ratio: 0.44; 95% confidence interval, 0.26–0.74; p=.002),” wrote the authors, led by first author Peter C. Albertsen, MD, of the University of Connecticut, Farmington.

The study was published in European Urology (2014; 65:565-73).

“Since our analysis is post hoc, our findings should only be interpreted as hypothesis generating,” they added.

Treatment with a GnRH antagonist appears “to halve the number of cardiac events experienced by men with pre-existing cardiovascular disease during the first year of androgen deprivation therapy when compared with GnRH agonists,” the authors concluded.

The study by Dr. Nguyen and colleagues was funded in part by the Prostate Cancer Foundation. Dr. Albertsen has consulted for Janssen Pharmaceuticald, Dendreon, and Ferring Pharmaceuticals. One of Dr. Albertsen’s co-authors is employed by Ferring Pharmaceuticals, and collection of data for the six prospective, randomized trials included in the study was funded by Ferring.

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