Androgen-deprivation therapy associated with increased risk of cardiac mortality in men with cardiovascular problems

Androgen-deprivation therapy (ADT) for prostate cancer was associated with a 5% absolute excess risk of cardiac-specific mortality at 5 years in men with congestive heart failure or prior myocardial infarction, a study found.

Researchers analyzed information on 5,077 men (median age, 69.5 years) with prostate cancer who were treated between 1997 and 2006. Thirty percent of these men (n=1,521) received neoadjuvant ADT for a median of 4 months. Neoadjuvant ADT included both a GnRH agonist and a nonsteroidal antiandrogen. Patients received depot formulations of leuprolide (7.5 mg/mo) or goserelin (3.6 mg/mo). Bicalutamide (50 mg/d) or flutamide (250 mg/8 h) was taken orally 1 to 3 days before starting the GnRH agonist.

Results appeared online Oct. 29 in BJU International.

After a median follow-up of 4.8 years, no association was detected between ADT and cardiac-specific mortality in men with no cardiac risk factors (1.08% at 5 years with ADT vs. 1.27% at 5 years without ADT; adjusted hazard ratio [HR], 0.83; 95% CI, 0.39 to 1.78; P=0.64). Also, there was no association in men with diabetes, hypertension, or hypercholesterolemia (2.09% vs 1.97%; adjusted HR, 1.33; 95% CI, 0.70 to 2.53; P=0.39).

However, ADT was associated with significantly increased cardiac death in men with congestive heart failure or myocardial infarction (adjusted HR, 3.28; 95% CI, 1.01 to 10.64; P=0.048). In this subgroup, the 5-year cumulative incidence of cardiac-specific mortality was 7.01% (95% CI, 2.82% to 13.82%) for ADT and 2.01% (95% CI, 0.38% to 6.45%) for no ADT, for a number needed to harm of 20.

The results are largely hypothesis-generating but can help doctors and patients weigh the benefits and risks of ADT, said a study author in a press release.

The author added 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,” the author said.