Does Comorbidity Influence the Risk of Myocardial Infarction or Diabetes During Androgen-Deprivation Therapy for Prostate Cancer?

Abstract

Background Androgen deprivation therapy for prostate cancer is associated with cardiovascular disease and diabetes. Some data suggest that men with certain conditions may be more susceptible to developing cardiovascular disease than others. Objective Assess whether the risk of myocardial infarction or diabetes during androgen deprivation therapy is modified by specific baseline comorbidities. Design, Settings and Participants Population-based observational study of 185,106 U.S. men aged ≥66 years diagnosed with local/regional prostate cancer from 1992 to 2007. We assessed comorbidities monthly over the follow-up period. Outcome Measurement and Analysis Cox proportional hazards models with time varying variables assessing incident diabetes or myocardial infarction. Results and limitations Overall, 49.9% received androgen deprivation therapy during follow-up. Among men with no comorbidities, androgen deprivation therapy was associated with an increase in the adjusted hazard of myocardial infarction (adjusted hazard ratio [AHR]=1.09, 95% confidence interval [CI]=1.02–1.16) and diabetes (AHR=1.33, 95% CI=1.27–1.39). Risk of myocardial infarction and diabetes were similarly increased among men with and without specific comorbid illnesses (all P for interactions >.10 with one exception). Previous myocardial infarction, congestive heart failure, peripheral arterial disease, stroke, hypertension, chronic obstructive pulmonary disease, and renal disease were associated with new myocardial infarction and diabetes, and obesity and rheumatologic disease were also associated with diabetes. Limitations include the observational study design, reliance on administrative data to ascertain outcomes, and lack of information on risk factors such as smoking and family history. Conclusions Traditional risk factors for myocardial infarction and diabetes were also associated with developing these conditions during androgen deprivation therapy but did not significantly modify the risk attributable to androgen deprivation therapy. Strategies to screen and prevent diabetes and cardiovascular disease in men with prostate cancer should be similar to those recommended for the general population.

Androgen deprivation therapy complications

“…Two studies included only men aged 66 years or older (Keating et al 2006, Alibhai et al 2009) while in the third cohort over 40% of the cohort were younger than 66 years . The risk of developing diabetes with ADT was independent of known risk factors (Keating et al 2013).…”

Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation therapy

“…Limitations include the lack of information on lifestyle factors and exact indications for palliative radiotherapy, and there may still be residual confounding, which could not be accounted for [13,32,33]. The selected proxies of disease progression, namely TURP, palliative radiotherapy and nephrostomy, may correspond to local or metastatic disease progression, but have been shown to be consistently associated with an increased risk of morbidity in this cohort [13].…”

Adverse effects of androgen deprivation therapy in patients with prostate cancer: focus on metabolic complications

“…65 A retrospective analysis, however, using data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) and including men with prostate cancer treated with radical prostatectomy followed or not with ADT found a significant correlation of ADT with increased CV mortality, but only among patients over 65 years old (p=0.002). 66 Furthermore, a recent meta-analysis of randomized controlled trials and observational studies showed that antiandrogen was associated with a 30% decreased risk for myocardial infarction compared to GnRH agonists, while combined androgen blockade was associated with a 10% increased risk for stroke when compared to antiandrogen.…”