Does Endocrine Therapy Increase the Risk of Cardiac Events in Men with Prostate Cancer?

In what is being touted as a practice-changing study, Mieke Van Hemelrijck, MD (pictured left), a cancer epidemiologist at King’s College, London, and associates found that men with locally advanced or metastatic prostate cancer who receive hormone therapy have a much greater risk of developing cardiac problems. They are also more likely to die from heart complications. These risks become evident within months of starting treatment.

Dr Van Hemelrijck’s team looked at data for 30,642 men treated for prostate cancer in Sweden from 1997 to 2006. All the men underwent endocrine therapy for locally advanced or metastatic disease. Some of the men received anti-androgen pills, which prevent testosterone from reaching the prostate. Others were given gonadotropin-releasing hormone (GNRH) agonist therapy or had their testicles removed, both of which dramatically reduce the circulating levels of testosterone. Slightly more than one-third of the men received both drugs.

“What we tried to do in our study,” Dr Van Hemelrijck said, “was basically look at different types of endocrine treatment but also different types of heart disease.” The investigators compared the incidences of ischemic heart disease, myocardial infarction, arrhythmia, and heart failure between the men with prostate cancer and other men in the database who were otherwise healthy. After accounting for age and preexisting heart disease, they found that the prostate cancer patients had increased risk of incidence or mortality in every category analyzed.

Increased Risk of Cardiac Conditions/Mortality Associated with Hormonal Therapy

Overall, %

Nonfatal heart attack

24

Arrhythmia

19

Ischemic heart disease

31

Heart failure

26

Fatal heart attack

28

Death from ischemic heart disease

21

Heart failure death

26

Fatal arrhythmia

5

The researchers said the risk of adverse cardiac effects or cardiac-related deaths were greatest for the men who received GNRH and lowest for men who only received anti-androgens. For example, men taking GNRHs were 34% more likely to suffer heart failure than healthy men and 30% more likely to develop ischemic heart disease. Compared with controls, men on anti-androgen therapy were only 5% more likely than controls to experience heart failure and 13% more likely to develop ischemic heart disease.

In a subset analysis, they stratified patients according to those who had preexisting heart conditions and those who did not. The risk of a cardiac event requiring hospitalization was much higher for patients without heart disease prior to starting hormone therapy. Dr Van Hemelrijck speculated that this might be because the men with heart disease were already on cardioprotective medications.

Dr Van Hemelrijck said because it was an observational study, the researchers could not make a definitive causal association between endocrine therapies and increased cardiac events. Despite this, she said the results show, “It is important to take heart disease into account…before starting prostate cancer patients on endocrine treatment.”

According to Dr Van Hemelrijck, many studies on the adverse affects associated with hormone-deprivation therapy have focused on metabolic changes, such as hot flashes. Heart disease has been gaining prominence as an area of research, but studies to date have been small or produced conflicting results. Based on her group’s findings, she hypothesized that “testosterone is protective for the heart…it can be that the risk for anti-androgens is less severe than for other treatments because there is still circulating testosterone.” She concluded that additional studies are needed, particularly experimental ones that evaluate the underlying biological mechanisms connecting testosterone to cardiac conditions.

For now, clinicians might want to consider these results when using endocrine therapy—particularly GNRH—to treat prostate cancer. Patients might require closer monitoring for the onset of cardiac conditions or physicians might want to consider taking preventive measures.

ECCO/ESMO Abstract 1BA