Association of androgen‐deprivation therapy with excess cardiac‐specific mortality in men with prostate cancer

Abstract

ObjectivesTo determine if androgen-deprivation therapy (ADT) is associated with excess cardiac-specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI). Patients and MethodsIn all, 5077 men (median age 69.5 years) with cT1c-T3N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant ADT (median duration 4 months) between 1997 and 2006. Fine and Gray competing risks analysis evaluated the association of ADT with CSM, adjusting for age, year of brachytherapy, and ADT treatment propensity score among men in groups defined by cardiac comorbidity. ResultsAfter a median follow-up of 4.8 years, no association was detected between ADT and CSM in men with no cardiac risk factors (1.08% at 5 years for ADT vs 1.27% at 5 years for no ADT, adjusted hazard ratio (AHR) 0.83; 95% confidence interval (CI), 0.39-1.78; P = 0.64; n = 2653) or in men with diabetes mellitus, hypertension, or hypercholesterolaemia (2.09% vs 1.97%, AHR 1.33; 95% CI 0.70-2.53; P = 0.39; n = 2168). However, ADT was associated with significantly increased CSM in men with CHF or MI (AHR 3.28; 95% CI 1.01-10.64; P = 0.048; n = 256). In this subgroup, the 5-year cumulative incidence of CSM was 7.01% (95% CI 2.82-13.82%) for ADT vs 2.01% (95% CI 0.38-6.45%) for no ADT. ConclusionADT was associated with a 5% absolute excess risk of CSM at 5 years in men with CHF or prior MI, suggesting that administering ADT to 20 men in this potentially vulnerable subgroup could result in one cardiac death.

Androgen deprivation therapy and cardiovascular complications

“…Authors also found that the risk for developing a CV disease was the highest during the fi rst 6 months of the treatment in men who experienced two or more cardiovascular events before they started the therapy with agonists of GnRH. This supports the opinion that those patients threated with ADT and an preexisting CV disease may be at the greatest risk (2)(3)(4)(5)33). Increased cardiovascular toxicity in patients undergoing a short-term ADT was confi rmed by another authors (38).…”

“…Unfortunately, ADT has also an adverse effects on cardiovscular system. According to several authors an increased attention should be given to patients with a history of cardiovascular problems (2)(3)(4)(5). The study by Keating et al (6) is one of the landmark studies investigating ADT associated cardiovascular risk.…”

Kosteneffektivität von GnRH-Antagonisten bei Patienten mit Prostatakarzinom und kardiovaskulärem Risiko

“…Aktuelle Studien und Übersichtsar-beiten legen nahe, dass unter ADT bei Patienten mit fPCa und einer KV-Vorgeschichte ein erhöhtes Risiko für erneute KV-Ereignisse besteht [6,20,30]. Dieses Risiko scheint zwischen den GnRHAgonisten Leuprorelin und Goserelin und -Antagonisten unterschiedlich ausgeprägt, wobei der etwas teurere GnRHAntagonist ein vorteilhafteres Risikoprofil aufweist [2].…”

Long-term Impact of Androgen Deprivation Therapy on Cardiovascular Morbidity after Radiotherapy for Clinically Localized Prostate Cancer

“…8,9,16 These tests for interaction did not reach significance for either patient age (P = .82) or history of pre-RT CE (P = .40).…”

“…In an analysis of randomized trial data, D'Amico et al reported increased risk of cardiac death after ADT among patients with moderate to severe comorbidity. 8 Publications from Nanda et al and Ziehr et al demonstrated that, in a cohort of 5077 men with clinically localized prostate cancer, ADT use increased all-cause mortality 9 and cardiac-specific mortality 16 only among patients with a prior history of congestive heart failure or acute MI. The authors of these studies reasonably conclude that, in patients with an already compromised cardiovascular status, ADT may precipitate cardiovascular mortality.…”