Cardiovascular disease risk and androgen deprivation therapy in patients with localised prostate cancer: a prospective cohort study

Abstract

Background:As androgen deprivation therapy (ADT) is increasingly being used in men with localised prostate cancer, our goal was to examine the association between ADT and the risk of cardiovascular disease (CVD).Methods:We conducted a prospective cohort study using records of a large health-care system in California. The study included men with newly diagnosed localised prostate cancer (1998–2008) who initially underwent active surveillance (N=7637) and were followed through 2010. We examined 10 individual CVD outcomes. Cox proportional hazard models incorporated time-varying treatment variables and controlled for race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication use, and CVD risk factors.Results:Of the 7637 subjects, nearly 30% were exposed to ADT. In the multivariable analyses, ADT was associated with an increased risk of heart failure (adjusted HR=1.81, 95% CI 1.40–2.32) in men without preexisting CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02–2.01), and conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed among patients with preexisting CVD.Conclusions:In men with clinically localised prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD. We also found an increased risk of arrhythmia and conduction disorder in men with preexisting CVD. This study provides the basis for identifying high-risk men treated with ADT who might benefit from regular cardiac monitoring and lifestyle modification recommendations.

Androgen Deprivation Therapy Use Increases the Risk of Heart Failure in Patients With Prostate Cancer: A Population‐Based Cohort Study

“…For instance, a cohort study conducted with records from a health-care delivery system in the United States indicated that androgen deprivation therapy users had a higher risk of developing heart failure compared with nonusers (adjusted HR, 1.27; 95%CI, 1.06-1.51). 21 One Chinese single-center observational study of 517 androgen deprivation therapy users and 228 nonusers found that 14 patients receiving androgen deprivation therapy were newly diagnosed with congestive heart failure, but no patient had congestive heart failure in the nonuser group, showing a greater risk of androgen deprivation therapy users to develop heart failure. 22 In addition, a nested case-control study in the United Kingdom found that usage of a combination of luteinizing hormone-releasing hormone (LHRH) agonists and antiandrogens was significantly associated with higher risk of incident heart failure (OR, 3.19; 95%CI, 1.10-9.27) compared with those who did not use these drugs.…”

“…[15][16][17][18][19] However, only a few studies have attempted to investigate the connection between androgen deprivation therapy and heart failure, and the relevant findings were inconsistent. [20][21][22][23][24] Three Western studies and one Chinese research study revealed a greater risk of heart failure with androgen deprivation therapy use. [21][22][23][24] A cohort study conducted in Canada found that androgen deprivation therapy was not associated with heart failure.…”

“…[20][21][22][23][24] Three Western studies and one Chinese research study revealed a greater risk of heart failure with androgen deprivation therapy use. [21][22][23][24] A cohort study conducted in Canada found that androgen deprivation therapy was not associated with heart failure. 20 Taken together, the previous literature showed conflicting evidence regarding the association between androgen deprivation therapy and heart failure.…”

“…To our knowledge, to date, most studies have only identified heart failure as the secondary outcome, rather than the primary outcome. 20,21 Some studies did not use propensity score-matched design to eliminate the potential bias. [21][22][23] In addition, only 1 single-center observational study recruited Asian patients as the study population.…”

“…20,21 Some studies did not use propensity score-matched design to eliminate the potential bias. [21][22][23] In addition, only 1 single-center observational study recruited Asian patients as the study population. 22 This is the first Asian populationbased study with a propensity score-matched strategy that intended to evaluate whether androgen deprivation therapy has an association with the subsequent risk of heart failure, using a population-based database in Taiwan.…”