Editing Hormonal Therapy (section)

=== Cardiovascular disease ===

* '''Conflicting findings between observational studies and secondary analyses of randomized trials'''; '''overall, sufficient evidence to suggest a link between use of ADT and CVD'''
** Cardiovascular mortality§
*** Meta-analyses of observational studies found significant increased risk
**** Observational studies limited by confounding
*** Meta-analyses of randomized trials found no significant association
**** Secondary analyses of randomized trials limited by power
** Nonfatal cardiovascular disease§
*** Meta-analyses of observational studies found significant increased risk
*** Meta-analyses of randomized trials found significant increased risk
** Myocardial infarction§
*** 1 meta-analysis of observational studies found significant increased risk, 1 found no significant association
*** Meta-analysis of randomized trials found no significant association
** Stroke§
*** Some meta-analyses of observational studies found significant increased risk, others did not
*** Meta-analysis of randomized trials found no significant association
** Venous thromboembolism
*** 2021 CUA Guidelines on ADT Adverse Events: Insufficient evidence to recommend routine use of venous thromboembolism prophylaxis in men receiving ADT.
* '''Pre-existing heart disease is significant risk factor for development of major adverse cardiac events (MACE) in men receiving ADT.'''
** MACE is defined as myocardial infarction, coronary revascularization, stroke, and hospitalization because of heart failure.
** '''Nanda et al. JAMA 2009'''
*** Population: 5077 males with localized or locally advanced prostate cancer treated with or without neoadjuvant ADT followed by RT
**** Median duration ADT 4 months
*** Primary outcome: all-cause mortality
*** Results:
**** No significantly increased risk of all-cause mortality in males with no comorbidity or a single coronary artery disease risk factor
**** Significantly increased risk of all-cause mortality in males with coronary artery disease–induced congestive heart failure or myocardial infarction
*** Nanda, Akash, et al."Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease–induced congestive heart failure or myocardial infarction." ''Jama'' 302.8 (2009): 866-873.
* '''GnRH agonist vs. antagonist'''
** Animal studies suggest that GnRH agonists, but not antagonists, may induce plaque instability and rupture
** Meta-analysis of randomized trials found that GnRH antagonists were associated with lower risk of cardiovascular events than GnRH agonists (HR 0.44 (95% CI 0.26 – 0.74)§
** HERO trial (see above) found that MACE occurs in 3% of patients randomized to relugolix compared to 6% of patients randomized to leuprolide§
** '''2021 CUA Guidelines on ADT Adverse Events: in males with a prior history of MI or stroke, consider use of a gonadotropin-releasing hormone (GnRH) antagonist'''
* '''Enzalutamide'''§
** Meta-analysis of observational studies found no significant increased risk of cardiac events
** Meta-analysis of randomized trials found no significant increased risk of cardiac events
** Significantly increased risk of hypertension
* '''Abiraterone'''§
** Meta-analysis of randomized trials found significant increased risk of cardiac events
** Pharmacovigilance study found significant increased risk of atrial tachyarrhythmia and heat failure§
* Trials underway to address cardiac outcomes in men receiving ADT
** PRONOUNCE
*** Population: males with advanced prostate cancer
*** Randomized to degarelix (GnRH antagonist) vs. leuprolide (GnRH agonist)
*** Primary outcome: time from randomization to MACE
** RADICAL-PC: RAndomizeD Intervention for Cardiovascular and Lifestyle Risk Factors in Prostate Cancer
*** Population: males with a new diagnosis of prostate cancer or recently initiated/about to initiate ADT
*** Randomized to systematic cardiovascular and lifestyle risk factor modification strategy vs. usual care
*** Primary outcome: time from randomization to MACE