AUA 2020: Cardiovascular Risk with GnRH Agonists and Antagonists: Real-world Data from UK Primary Care

( Androgen deprivation therapy in prostate cancer is an effective treatment for a certain period of time and does improve prognosis. However, there is concern over long term side effects, including cardiovascular events. It has been shown that long-term androgen deprivation therapy increases the cardiovascular event rate. 20 to 30% of prostate cancer patients have pre-existing cardiovascular disease, and their prognosis has been shown to be worse as they may have a greater increase in cardiovascular risk when started therapy with androgen deprivation therapy.

It has also been shown that pre-existing cardiovascular disease increases the risk of death in prostate cancer patients, as can be seen in Table 1.

Table 1 – Increased risk of death in prostate cancer patients with pre-existing cardiovascular disease:


It has also been shown that compared to the normal male population, men treated with ADT are at an increased risk for cardiovascular events (Figure 1).

Figure 1 – Cardiovascular outcomes of prostate cancer patients treated with ADT compared to normal male population:


There is also data showing that the cardiovascular risk may depend on the type of ADT being used, with bilateral orchiectomy showing a lower rate of cardiovascular events than LHRH agonists (Table 2).


Table 2- Cardiovascular risk is affected by the type of ADT used:

It is not clear whether there is a lower cardiovascular risk with GnRH antagonists compared to LHRH agonists. In a pooled trial data, it was shown that there is a lower cardiovascular event rate with the antagonists when compared to agonists. When assessing patients with no cardiovascular disease at baseline, there was no difference in the cardiovascular event rate between the treatment groups. However, when there was a cardiovascular disease at baseline, there was a 56% relative risk reduction of a cardiovascular event with the GnRH antagonist compared to the GnRH agonist. There was also an 8.2% absolute risk reduction of a cardiovascular event or death with the GnRH antagonist. The number needed to treat was 12 to prevent one cardiovascular event(1).

The presented study's aim was to clarify whether the cardiovascular risk in prostate cancer patients is, as suggested, lower in patients treated with GnRH antagonists compared to GnRH agonists. The authors used real-world data acquired from the Optimum Patient Care Database (ODCPR) – a UK primary care database, consisting of over 700 general practitioners' practices, consisting of records from 8.8 million patients.

In this study, patients with prostate cancer who were new users of GNRH antagonists and GnRH agonists were identified. The relative risk of cardiovascular events, including heart failure, myocardial infarction, arrhythmia, and ischemic heart disease for both types of treatments was determined.

The baseline characteristics of the patients analyzed in this study are shown in Table 3, and the relative risk of degarelix (GnRH antagonist) vs. GnRH agonists is shown in Figure 2.

Table 3 – Baseline characteristics:


Figure 2 – Relative risk of Degarelix vs. GnRH agonists:


The authors concluded that this study showing real-world data, demonstrated findings that are consistent with previous studies, showing a lower cardiovascular risk with GNRH antagonists when compared to GnRH agonists. The authors believe that, especially in men with a pre-existing cardiovascular disease, the use of an antagonist rather than an agonist, may lower cardiovascular risk over time. The authors concluded their presentation with a suggested algorithm of assessment and mitigation of cardiovascular risk in clinical practice (Figure 3).


Figure 3 – Suggested assessment and mitigation of cardiovascular risk in clinical practice:



Presented by: Patrick Davey, MD, Consultant Cardiologist, Northampton General Hospital NHS Trust, Oxford, Great Britain

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, @GoldbergHanan at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020


1. Albertsen PC, Klotz L, Tombal B, Grady J, Olesen TK, Nilsson J. Cardiovascular morbidity associated with gonadotropin-releasing hormone agonists and an antagonist. Eur Urol. 2014;65(3):565-73


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