AUA 2018: Cardiovascular Events and Biomarkers in a Randomized Trial Comparing LHRH Agonist and Antagonist Among Patients with Advanced Prostate Cancer

San Francisco, CA ( Androgen-deprivation therapy (ADT) used in prostate cancer patients may increase their risk of cardiovascular events. There has been data suggesting that LHRH-antagonist may be associated with lower risk of these events compared to LHRH agonists. The authors hypothesized a role for FSH in mediating ADT induced atherosclerosis. In this current presentation, the authors report biomarkers of cardio-vascular events and outcomes from a randomized controlled study.

This was a bi-centeral randomized open-label study of the use of Degarelix compared to LHRH agonists among prostate cancer patients with pre-existing cardiovascular disease, scheduled to start ADT for at least a year. A Cardiovascular event was considered one of the following: 

  1. Myocardial infarction
  2. Ischemic or hemorrhagic cerebrovascular event
  3. Arterial embolic and thrombotic event
  4. Emergency room visit or hospitalization due to ischemic heart disease conditions
  5. Coronary artery or iliofemoral artery revascularization (percutaneous or surgical procedures)
  6. Peripheral vascular disease event (vascular surgery/intervention)
These events were prospectively collected. Serum levels for hormonal profile and biomarkers including NT-proBNP, DDimer, HS-Troponin and CRP were taken at baseline and every three months.

A total of eighty patients were enrolled (39 randomized to antagonist and 41 agonists), with a median follow up of 10 months. No difference in age, stage of prostate cancer and baseline cardiovascular status were observed between the two arms. During follow-up, 14 patient developed a new cardiovascular event. Eight of the 14 patients were hospitalized due to ischemic heart disease, one patient suffered from a myocardial infarction and two from a new ischemic cerebrovascular event. Twenty-eight percent (n=11) of patients randomized to LHRH agonist had a cardiovascular event compared to 7% (n=3) of those randomized to antagonists (log rank p=0.008) (Figure 1). Baseline levels of serum NT-proBNP, a well-known cardiac biomarker, was able to predict events (AUC= 0.69, 95% CI 0.56-0.84, p=0.003). However, baseline D-Dimer, HS-Troponin and CRP were not predictive. In addition, patients with less than a 60% decrease in FSH levels during the first three months of treatment had a higher risk of developing a cardiovascular event ( 40% vs 10%, p=0.005).

Figure 1 – Kaplan-Meier curves: Time to first cardiovascular (CV) event and time to first Major adverse cardiovascular and cerebrovascular event (MACCE):
UroToday AUA2018 Kaplan Meier curves

In this interesting study, the authors concluded that cardiovascular events may develop early in patients receiving LHRH-agonist compared to an antagonist. Baseline NT-proBNP may predict the cardiovascular outcome. These events could be potentially linked to the reduced suppression of FSH during ADT.

Presented by: David Margel, Rabin Medical Center, Israel
Co-Author: Petach Tikva, Israel, Avivit Pe'er, Haifa, Israel, Yaara Ber, Petach Tikva, Israel, Marina Shaparberg, Haifa, Israel, Sivan Sela, Rachel Ozalvo, Tzlil Tabachnik, Petach Tikva, Israel, Wilhelmina Duivenvoorden, Jack Baniel, Petach Tikva, Israel, Jehonathan Pinthus, Hamilton, Canada,

Written by:  Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA