Can degarelix (Gonadotropin-releasing hormone antagonist) cause a heart attack, particularly in patients with pre-existing cardiovascular disease, hypertension, diabetes, or high cholesterol?

Degarelix and Cardiovascular Risk: Heart Attack Potential

Degarelix may have a lower risk of cardiovascular events compared to traditional GnRH agonists, but patients with pre-existing cardiovascular disease remain at significantly elevated risk for heart attacks and other cardiac events during treatment.

Understanding the Cardiovascular Risk Profile

The cardiovascular safety of degarelix differs importantly based on your baseline cardiac health:

For Patients WITHOUT Pre-existing Cardiovascular Disease

• Degarelix appears relatively safe in men without prior cardiovascular disease, with event rates of 4.3 per 100 person-years, which is not significantly different from pre-treatment rates 1
• Real-world UK data demonstrates that degarelix confers a significantly lower risk of cardiac events compared to GnRH agonists (risk ratio: 0.39,95% CI 0.191-0.799) 2
• In the general population receiving degarelix, cardiovascular event rates were similar before and after treatment initiation (5.5 vs 6.1 per 100 person-years) 1

For Patients WITH Pre-existing Cardiovascular Disease

This is where the critical risk emerges:

• Event rates nearly doubled after degarelix treatment in men with baseline cardiovascular disease (5.3 to 10.5 events per 100 person-years, p=0.0013) 1
• Prior history of heart attack or stroke is the strongest independent predictor of treatment-onset major adverse cardiovascular events (MACE), with a hazard ratio of 5.32 (95% CI 3.36-8.42) 3
• Pre-existing cardiovascular disease was the most powerful predictor of events on multivariate analysis, even more than age or other risk factors 1

Comparative Safety: Degarelix vs. GnRH Agonists

Degarelix may offer cardiovascular advantages over traditional GnRH agonists:

• The most frequently reported cardiac disorder was ischemic heart disease, occurring in 4% of degarelix-treated patients vs. 10% of leuprolide-treated patients 4
• A 12-month randomized controlled trial showed similar cardiovascular safety profiles between degarelix and leuprolide, with no significant differences in QT interval changes or arrhythmias 4
• However, the evidence for superiority is mixed, with one recent study showing no significant difference in MACE rates between relugolix, degarelix, and leuprolide in the post-2020 era 3

Additional Risk Factors That Amplify Cardiovascular Danger

Beyond pre-existing cardiovascular disease, these factors independently increase your risk:

• Older age significantly increases cardiovascular event risk (p=0.0459) 4
• Higher systolic blood pressure at baseline (p=0.0061) 4
• Obesity 1
• Alcohol abstinence (paradoxically) 1
• Higher Charlson Comorbidity Index (HR=1.12 per point increase, 95% CI 1.06-1.18) 3

Critical Clinical Implications

Pre-Treatment Cardiovascular Screening is Essential

Before starting degarelix, you must:

• Undergo comprehensive cardiovascular risk stratification to identify known or underlying vascular disease 2
• Document any history of myocardial infarction, stroke, peripheral arterial disease, or prior revascularization 3
• Measure baseline blood pressure and assess for hypertension 4
• Calculate your Charlson Comorbidity Index 3

Ongoing Cardiovascular Management During Treatment

If you have cardiovascular risk factors or disease:

• Implement appropriate lifestyle modifications and pharmacological interventions to mitigate cardiovascular risk 2
• Establish regular cardiology follow-up—critically, 27% of high-risk patients in one study lacked cardiology or primary care during ADT and did not receive cardio-protective therapies 3
• Monitor cardiovascular risk factors and treatment response at regular intervals 2
• Consider that 55% of patients with prior MACE were managed by cardiology during ADT, compared to only 23% without prior MACE 3

Important Caveats and Limitations

• Maximum follow-up in available studies was only 14 months, which is relatively short for assessing long-term cardiovascular outcomes 5
• The evidence base lacks data on overall survival and cancer-specific survival comparing degarelix to standard androgen suppression 5
• Degarelix likely results in increased injection site pain compared to GnRH agonists (RR 15.68,95% CI 7.41-33.17), though this is not a cardiovascular concern 5
• The mechanism appears to be hypogonadism-related rather than a direct drug effect, as both degarelix and leuprolide show similar cardiovascular profiles in controlled settings 4

The Bottom Line for Clinical Decision-Making

Degarelix does not directly "cause" heart attacks in the traditional sense, but it significantly amplifies pre-existing cardiovascular risk through testosterone suppression. If you have established cardiovascular disease (prior heart attack, stroke, or significant vascular disease), your risk of experiencing another cardiovascular event approximately doubles during degarelix treatment 1. However, degarelix may still be preferable to GnRH agonists in this high-risk population, given the lower relative risk observed in real-world data 2. The key is aggressive cardiovascular risk management before and during treatment, with close cardiology involvement for anyone with prior cardiac events 3, 2.