Androgen Deprivation Therapy and Cardiovascular Disease Incidence in Young Nonmetastatic Prostate Cancer Patients: A Nationwide Database Study

Abstract

Androgen deprivation therapy (ADT) is commonly used in patients with metastatic disease, locally advanced or high risk prostate cancer (PCa). There is conflicting evidence regarding the association between ADT and cardiovascular disease (CVD). Most studies have examined men >65 years, who have a higher risk of CVD. This study aims to understand the relationship between ADT and CVD risk in younger men (40 to 64 years). Retrospective review of a national health insurance claims database of privately insured individuals (MarketScan) from January 1 to December 31, 2011 identified 124,164 newly diagnosed PCa patients. The patients were followed through December 31, 2014. The study included 24,631 non-metastatic PCa patients after applying exclusion criteria. All participants were free of CVD before January 1st, 2011. In full cohort study, we identified 1522 PCa patients receiving >=3months of pharmacologic ADT or orchiectomy as the study cohort and 23,109 PCa patients with no ADT/<3months of ADT as the comparison cohort. The primary end point was CVD, a composite of coronary artery disease (CAD), myocardial infarction (MI) and stroke, identified using ICD-9-CM codes. Multivariable Cox proportional hazards models were used to assess CVD risk among PCa patients on pharmacologic ADT>=3months/orchiectomy and no ADT/<3months of ADT groups adjusting for potential confounders such as age, region, residence, diabetes, hypertension, hyperlipidemia, prostatectomy, and radiation therapy. Sensitivity analyses were performed based on type and duration of ADT. The mean age of PCa patients with ADT>=3months/orchiectomy was 57.02±3.56 years and the no ADT/<3months of ADT group was 56.16± 4.22 years. We identified 3376 incident CVD cases during 2012-2014. In full cohort study, pharmacologic ADT>=3months/orchiectomy was associated with higher risk of developing CVD compared to no ADT/<3months of ADT, adjusted HR (aHR) 1.27; 95% CI (1.13 to 1.43). Treatment with GnRH agonists was associated with increased incidence of CAD (aHR 1.39; 95% CI, 1.14 to 1.68) and stroke ((aHR 1.65; 95% CI, 1.28 to 2.11), except for MI (aHR 1.05; 95% CI, 0.60 to 1.83). Similarly, combined androgen blockade was also associated with an increased risk of incident CAD (aHR 1.33; 95% CI, 1.10 to 1.61) and stroke (aHR 1.63; 95% CI, 1.28 to 2.07) except for MI (aHR 1.03; 95% CI, 0.60 to 1.77). Furthermore 1 to 2 years of ADT duration was associated with 61% higher risk of CAD (aHR 1.61; 95% CI, 1.14 to 2.28) and 72% higher risk of stroke (aHR 1.72; 95% CI, 1.07 to 2.75) except for MI (aHR 1.60; 95% CI, 0.65 to 3.92) In this large study of nonmetastatic PCa patients younger than age 65, there was higher incidence of CVD in patients with ADT >=3months/orchiectomy compared to no ADT/<3months of ADT. Longer duration of ADT was positively associated with increased risk of CAD and stroke.