Cardiovascular Risk Profile in Prostate Cancer Patients Treated with GnRH Agonists versus Antagonists: An Italian Real-World Analysis

Abstract

Purpose

To evaluate and compare the incidence of cardiovascular (CV) events in a large contemporary cohort of patients diagnosed with prostate cancer (PCa) and in treatment with GnRH agonists or GnRH antagonists.

Patients and Methods

An Italian observational retrospective cohort study based on administrative databases of three local health units and two Regions was performed. PCa patients treated with GnRH agonists or antagonist were included between January 01, 2013 and December 31, 2016. Index date (ID) was the date of first GnRH agonist/antagonist prescription during inclusion period. Follow-up was from ID to December 31, 2017. Patients were excluded if they were under abiraterone treatment or combination therapy with antiandrogens during follow-up. The incidence rate of CV events (acute myocardial infarction, ischemic heart diseases, cerebrovascular diseases, cardiac dysrhythmias, heart failure, atherosclerosis, aneurism, other CV-related conditions) was calculated among patients not switching to androgen deprivation therapy (ADT) in the overall cohort and in a sub-cohort of patients without previous CV events.

Results

In total, 9785 (mean age 76.8 ± 8.5) patients were included: 9158 (93.6%) were treated with a GnRH agonist and 627 (6.4%) with a GnRH antagonist. Of them, 9627 did not switch to ADT and were considered in the analyses. The incidence of CV events was significantly higher in patients treated with GnRH agonists rather than antagonists (8.8 vs 6.2, p=0.002). Mean time to CV event was beyond 1 year of treatment in both groups. In the multivariable regression analysis, the risk of experiencing CV events was significantly lower in patients treated with GnRH antagonist rather than those treated with GnRH agonists [HR (95% CI): 0.76 (0.60–0.95), p=0.018]. These findings were confirmed in the sub-cohort of patients without previous CV events.

Conclusion

This Italian observational study shows that most patients received a GnRH agonist rather than a GnRH antagonist prescription. GnRH antagonist seems to have a better CV risk profile than GnRH agonist, both in patients with and without a history of CV events.

Keywords:

• cardiovascular events
• GnRH agonists
• GnRH antagonist
• prostate cancer
• real-world setting

Acknowledgments

Manuscript development was supported by unconditional funding from Ferring Pharmaceuticals.

Disclosure

The views expressed here are those of the authors and not necessarily those of the supporters. The agreement signed by Clicon S.r.l. and Ferring Pharmaceuticals does not create any entityship, joint venture or any similar relationship between parties. Clicon S.r.l. is an independent company. Neither Clicon S.r.l. nor any of their representatives are employees of Ferring Pharmaceuticals for any purpose. MO has worked as a consultant for Ferring and reports personal fees from Ferring, during the conduct of the study; personal fees from Janssen and Takeda, outside the submitted work. The authors report no other conflicts of interest in this work.