Androgen Deprivation Therapy and Cardiovascular Risk

Abstract

A B S T R A C T PurposeThe potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to further elucidate the association between treatment selection and cause of mortality. Patients and MethodsA total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer-specific mortality (PCSM), CVM, and all-cause mortality. A propensity score-adjusted and a propensitymatched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments. ResultsPatients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT. ConclusionPatients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.

Fifth Joint Meeting of J-CaP and CaPSURE: Advancing the Global Understanding of Prostate Cancer and Its Management

“…age or co-morbidity, might be contributing to CV risk. These data were also analyzed using propensity scoring-a measure of the patient's probability of receiving treatment (ADT), conditional on important clinical and sociodemographic covariates (21). No differences in CV mortality were noted between those who did and did not receive ADT inferring that unmeasured variables-which influence treatment decision-making but are not recorded in CaPSUREmight have confounded the association between ADT and CV mortality in many previous studies.…”

Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications

“…Based on propensitymatching algorithm, there was no significant difference in CV mortality among men who did versus who did not receive ADT. 36 A few studies have also contradicted the association of ADT with cerebrovascular disease. The first study found that men on ADT were less likely to experience a stroke than men not undergoing ADT.…”

“…35 Among these men, the cumulative CV mortality at 7 years was 2.6% for men not undergoing ADT, 2.1% for men with ,6 months ADT and 1.4% for men undergoing ADT for .6 months. Punnen et al 36 analyzed a total of 7248 men in the Cancer of the Prostate Strategic Urologic Research Endeavor registry to assess the relationship between ADT and CV mortality. Competing hazard survival analysis was performed for PCa-specific, CV and all-cause mortality.…”

Metabolic syndrome in patients with prostate cancer undergoing intermittent androgen-deprivation therapy

“…32 Punnen et al also analyzed a total of 7248 men to assess the relationship between ADT and CV mortality and found that there was no significant difference in CV mortality among men who did vs. those who did not receive ADT. 33 Although the relationship between ADT and CVD is controversial, many authors have shown that the profound hypogonadism in patients undergoing ADT may be responsible for high CV mortality. Low testosterone levels are a risk factor for metabolic syndrome and metabolic syndrome is also a known cause of increased CV mortality.…”