Can Degarelix (Gonadotropin-releasing hormone antagonist) cause cardiac events?

Can Degarelix Cause Cardiac Events?

Yes, degarelix can cause cardiac events, particularly QT interval prolongation, and the FDA label specifically warns that androgen deprivation therapy may prolong the QT interval, requiring careful consideration in patients with congenital long QT syndrome, congestive heart failure, or frequent electrolyte abnormalities. 1

FDA-Labeled Cardiovascular Warnings

The FDA drug label for degarelix (FIRMAGON) contains explicit warnings about cardiovascular risks:

• QT interval prolongation is a recognized risk with androgen deprivation therapy including degarelix, requiring providers to weigh benefits against risks in high-risk patients 1
• Periodic monitoring of electrocardiograms and electrolytes should be considered, particularly in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, or those taking QT-prolonging medications 1
• In the pivotal trial comparing degarelix to leuprolide, three patients (<1%) in the degarelix group had QTcF ≥500 msec, with a median QT change of 12.3 msec from baseline 1
• Electrolyte abnormalities should be corrected before initiating therapy 1

Conflicting Evidence on Major Adverse Cardiovascular Events

The evidence regarding major adverse cardiovascular events (MACE) with degarelix is contradictory and depends on study design:

Meta-analyses Suggesting Lower Risk

• A 2024 meta-analysis of 15 studies with 123,969 patients found degarelix was associated with significantly lower incidence of MACE compared to GnRH agonists (RR 0.59; 95% CI 0.41-0.84; p=0.003) 2
• A 2021 UK real-world study demonstrated significantly lower cardiac event risk with degarelix versus GnRH agonists (risk ratio 0.39; 95% CI 0.191-0.799; p=0.01) 3

Recent Evidence Suggesting Higher Risk

• A 2025 systematic review of real-world evidence studies found degarelix associated with increased MACE risk (pooled RR 1.31; 95% CI 1.14-1.51), particularly among patients with pre-existing cardiovascular disease (pooled RR 1.31; 95% CI 1.11-1.56) 4
• This increased risk may reflect confounding by indication, as high-risk patients are preferentially treated with degarelix 4

Prospective Trial Data

• Analysis of 1,704 men across 9 clinical trials showed cardiovascular event rates were similar before and after degarelix treatment in the total population (5.5 vs 6.1/100 person-years, p=0.45) 5
• However, event rates appeared higher after degarelix in men with baseline cardiovascular disease (5.3 to 10.5 events per 100 person-years, p=0.0013) 5
• Pre-existing cardiovascular disease was the strongest independent predictor of events, followed by older age, alcohol abstinence, and obesity 5

Clinical Algorithm for Risk Assessment

Pre-Treatment Evaluation

• Screen all patients for cardiovascular disease history including myocardial infarction, stroke, TIA, angina, congestive heart failure, and arrhythmias 5, 4
• Obtain baseline ECG in patients with known cardiac risk factors or history of cardiovascular disease 1
• Check baseline electrolytes (potassium, magnesium, calcium) and correct abnormalities before initiating therapy 1
• Assess for congenital long QT syndrome through personal and family history 1

High-Risk Patient Identification

Patients requiring heightened vigilance include those with:

• Pre-existing cardiovascular disease (strongest predictor of events) 5, 4
• Congenital long QT syndrome or QTc >500 msec 1
• Congestive heart failure 1
• Frequent electrolyte abnormalities 1
• Concurrent QT-prolonging medications 1
• Older age and multiple cardiovascular risk factors 5

Monitoring Strategy

• Consider periodic ECG monitoring during treatment, particularly in the first 3-6 months 1
• Monitor electrolytes regularly in patients with risk factors for imbalances 1
• Assess for cardiovascular symptoms at each visit, including chest pain, palpitations, syncope, or dyspnea 1

Common Pitfalls and Caveats

• The most common adverse reaction is injection site pain (RR 15.68; 95% CI 7.41-33.17), occurring in approximately 440 more patients per 1000 compared to GnRH agonists 6
• Serious adverse events overall appear similar between degarelix and standard androgen suppression (RR 0.80; 95% CI 0.62-1.05) 6
• Maximum follow-up in most trials is only 14 months, which is insufficient to fully characterize long-term cardiovascular risk 6
• Residual confounding by indication likely explains some of the increased cardiovascular risk seen in real-world studies, as clinicians may preferentially use degarelix in higher-risk patients 4
• Quality of life appears similar between degarelix and GnRH agonists 6