Androgen deprivation therapy problematic for prior heart attack victims

by Bruce Sylvester: Men who have had a heart attack and then receive androgen deprivation therapy (ADT) for prostate cancer are at an increased risk of subsequent fatal heart attack, researchers reported in a research letter in the September 22/29, 2015 issue of Journal of the American Medical Association (JAMA).

“These findings give us reason to rethink how we manage prostate cancer in men with known heart disease,” said Anthony D’Amico, MD, lead author and chief of genitourinary radiation oncology at Brigham and Women’s Hospital in Boston. “Specifically, we should be cautious in prescribing ADT in all men who have had a prior heart attack. Men with significant heart disease that is not amenable to medical or surgical correction may be best served with RT alone.”

As background, the authors noted that ADT and radiation therapy prolong survival in unfavorable-risk prostate cancer and are the standard of care. But in 2008 the FDA issued a “black box” warning about ADT use for prostate cancer after evidence emerged showing an increased risk of  subsequent non-fatal cardiovascular events. An association of ADT and fatal heart attacks has to date remained uncertain.

In the new study, investigators compared overall survival and mortality due to prostate cancer, fatal heart attack and all other causes in a group of 206 men with unfavorable risk prostate cancer who had been randomized to radiation monotherapy or to radiation and six months of ADT. Average age was 76 years.

The subjects were evaluated according prior comorbidity, including prior heart attack.

After a median of 16 years follow-up, overall survival did not differ between the radiation-only and radiation-plus-ADT groups of men.

But analysis by comorbidity subgroups showed that, while radiation-plus-ADT prolonged survival in men with no or minimal comorbidity, among subjects with a prior heart attack radiation-plus-ADT therapy was associated with shortened survival at a statistically significant rate (P < .001) due to a higher rate of fatal heart attacks

“While there is a growing body of evidence to support active surveillance for men with low risk prostate cancer, men who have unfavorable-risk cancer and significant comorbidity, notably heart disease, may be best served by considering RT [radiation therapy] alone or possibly active surveillance. For these men, the side effects of ADT may be life threatening. More research is needed to better understand the newer forms of hormone therapy that do not lower testosterone and how they impact survival,” D’Amico added.