What is the clinical evidence from this study?

Study design: Cohort. Population: Prostate cancer (n=20216). Intervention: Androgen deprivation therapy (ADT) vs. Untreated patients (active surveillance or watchful waiting). Primary outcome: Cardiovascular event (death from cardiovascular disease or hospitalisation for cardiovascular disease) (HR 1.25, 95% CI 1.16-1.35).

October 25, 2019Open Access

The Risk of Cardiovascular Disease in Prostate Cancer Patients Receiving Androgen Deprivation Therapies

Key Result

Androgen deprivation therapy was associated with a 25% increase in cardiovascular events (HR 1.25) compared with untreated patients, reflecting increases with GnRH agonists and degarelix.

Study Design

Type

Cohort (n=20,216)

Multicenter

Yes

Structured PICO

Does androgen deprivation therapy increase the risk of cardiovascular events in men newly diagnosed with prostate cancer?

Population

20,216 men newly diagnosed with prostate cancer between 2009 and 2015 in Scotland.

Intervention

Androgen deprivation therapy (ADT) including GnRH agonists (goserelin, leuprorelin, triptorelin, histrelin), the GnRH antagonist degarelix, bicalutamide monotherapy, and other antiandrogens, analyzed as a time-varying exposure.

Comparator

Untreated patients (receiving active surveillance or watchful waiting).

Outcome

Cardiovascular event consisting of either death from cardiovascular disease or hospitalisation for cardiovascular disease.composite

In a real-world cohort of prostate cancer patients, androgen deprivation therapy with GnRH agonists or degarelix was associated with a significantly increased risk of cardiovascular events, whereas bicalutamide monotherapy was not.

Main Result

Effect estimate: HR 1.25 (95% CI 1.16-1.35)

Limitations

Possibility of residual confounding by incompletely recorded (stage, Gleason score) or unavailable variables (obesity, smoking, alcohol intake)
ADT use was determined from dispensing records and medication adherence cannot be confirmed
Patients receiving ADT may have increased exposure to health care professionals increasing the likelihood of cardiovascular disease being identified

Abstract

BACKGROUND: Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting. METHODS: We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease. RESULTS: The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3). CONCLUSIONS: There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.

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