To examine and quantify the contemporary association between androgen-deprivation therapy (ADT) and three separate endpoints: coronary artery disease (CAD), acute myocardial infarction (AMI), and sudden cardiac death (SCD), in a large USA contemporary cohort of patients with prostate cancer.

In all, 140 474 patients diagnosed with non-metastatic prostate cancer between 1995 and 2009 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database were abstracted. Patients treated with ADT and those not receiving ADT were matched using propensity score methodology. The 10-year CAD, AMI, and SCD rates were estimated. Competing-risks regression analyses tested the association between the type of ADT (GnRH agonists vs bilateral orchidectomy) and CAD, AMI, and SCD, after adjusting for the risk of dying during follow-up.

Overall, the 10-year rates of CAD, AMI, and SCD were 25.9%, 15.6%, and 15.8%, respectively. After stratification according to ADT status (ADT-naïve vs GnRH agonists vs bilateral orchidectomy), the CAD rates were 25.1% vs 26.9% vs 23.2%, the AMI rates were 14.8% vs 16.6% vs 14.8%, and the SCD rates were 14.2% vs 17.7% vs 16.4%, respectively. In competing-risks multivariable regression analyses, the administration of GnRH agonists (all P < 0.001), but not bilateral orchidectomy (all P ≥ 0.7), was associated with higher risk of CAD, AMI, and SCD.

The administration of GnRH agonists, but not orchidectomy, is still associated with a significantly increased risk of CAD, AMI, and, especially, SCD in patients with non-metastatic prostate cancer. Alternative forms of ADT should be considered in patients at higher risk of CV events.