Impact of New Hormonotherapy Drugs in Prostatic Cancer on the Risk of Cardiovascular Events : a Pharmacoepidemiology Study Using the French Health Care Claims Database

Active, not recruiting

• Conditions: Prostate Cancer

• Registration Number: NCT06902441
• Lead Sponsor: University Hospital, Caen

Brief Summary

In prostate cancer, whether in advanced or localized cases, hormone therapy is a key treatment. These treatments reduce male hormone levels to slow cancer growth.

More recently, a new class of drugs called Androgen Receptor Signaling Inhibitors (ARSIs) has been introduced. These drugs are used alongside standard hormone therapy and are now given to both advanced and high-risk localized prostate cancer patients.

There are two main types of ARSIs: abiraterone acetate, which blocks androgen production, and enzalutamide, apalutamide, and darolutamide, which prevent cancer cells from using androgens. Doctors choose between these treatments based on patient needs, as no single drug has been proven superior. These therapies have significantly improved patient survival.

However, studies show that 30% of prostate cancer patients die from heart-related problems, a higher rate than in the general population. It is important to understand the link between these treatments and heart risks.

One study found that all ARSIs increase the risk of serious heart issues. However, it did not consider patients' previous heart conditions, which are known to affect heart risk with abiraterone and enzalutamide.

For this reason, we are conducting a study using a large real-world database to compare the heart risks of abiraterone, enzalutamide, and apalutamide while considering patients' existing heart conditions and treatment duration.

Detailed Description

In prostate cancer, both in metastatic settings and in many localized cases, androgen suppression via GnRH agonists or antagonists remains the cornerstone of treatment. These androgen deprivation therapies (ADT) aim to reduce circulating androgen levels.

In recent years, Androgen Receptor Signaling Inhibitors (ARSIs) have emerged, prescribed in combination with standard androgen suppression therapy (ADT). These treatments have broad indications in metastatic settings and are now also used in localized high-risk prostate cancer.

A conventional distinction is made between abiraterone acetate, a selective inhibitor of androgen synthesis that blocks CYP 17, and other NGHTs that inhibit the androgen receptor, namely enzalutamide, apalutamide, and darolutamide. The indications for these treatments are often similar, with no clear evidence of superiority of one over another. For instance, in synchronous metastatic castration-sensitive prostate cancer, when treated with NGHTs combined with AST, clinicians may choose between abiraterone acetate, apalutamide, or enzalutamide. Thus, the safety profile of these treatments plays a crucial role in therapeutic decision-making. These new hormonal therapies have significantly improved patient survival.

However, when examining the causes of death among prostate cancer patients, studies have shown that 30% of deaths are due to cardiovascular causes, with an excess risk compared to the general population. It is therefore essential to investigate these cardiovascular events and their associations with administered treatments.

The meta-analysis by El-Taji et al. identified an increased risk of high-grade cardiovascular toxicities for all next-generation hormonal therapies (HR 1.75; 95% CI: 1.50-2.04). This excess risk was observed for each ARSI individually. However, this meta-analysis could not account for patients' cardiovascular history, despite demonstrated associations between pre-existing cardiovascular conditions and the risk of cardiovascular toxicity with abiraterone acetate and enzalutamide.

For these reasons, we have decided to compare cardiovascular toxicities associated with abiraterone, enzalutamide, and apalutamide using a large real-world database, taking into account pre-existing cardiovascular comorbidities as well as treatment exposure duration.

Study Timeline

• Study Start: 2025-01-07
• Status Verified: 2025-03
• Study First Submitted: 2025-03-24
• Study First Submitted QC: 2025-03-24
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-30
• Last Update Posted: 2025-03-30
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 52000

Inclusion Criteria

• Patients had to begin a treatment with Enzalutamide, Abiraterone or Apalutamide between the 01-01-2018 and the 31-12-2022
• Patients must have a unique ID in the database, to be able to link the data

Exclusion Criteria

• Previous treatment with another novel androgen receptor signaling inhibitors
• Patients were excluded if they began a chemotherapy treatment in the 6 weeks following the beginning of ARSI

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Risk of hospitalization for cardiovascular cause	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023) or outcome	The primary objective of this study was to compare the risk of hospitalization for cardiovascular reasons among the different ARSIs. This outcome was evaluated by the occurrence of a hospitalization for one of these reasons as the principal diagnosis in the French PMSI.

Secondary Outcome Measures

Name	Time	Method
Risk of hospitalization for hearth failure	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023) or outcome	One of the secondary objective of this study was to compare the risk of hospitalization for heart failure amoung the different ARSIs. This outcome was evaluated by the occurrence of a hospitalization for heart failure as the principal diagnosis in the French PMSI (ICD-10 code I50)
Risk of hospitalization for atrial fibrillation	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023) or outcome	One of the secondary objective of this study was to compare the risk of hospitalization for atrial fibrillation or flutter amoung the different ARSIs. This outcome was evaluated by the occurrence of a hospitalization for atrial fibrillation or flutter as the principal diagnosis in the French PMSI (ICD-10 code I48)
Risk of hospitalization for ischemic heart disease	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023) or outcome	One of the secondary objective of this study was to compare the risk of hospitalization for ischemic heart disease amoung the different ARSIs. This outcome was evaluated by the occurrence of a hospitalization for ischemic heart disease as the principal diagnosis in the French PMSI (ICD-10 code I20-I25)
Risk of hospitalization for successfully resuscitated cardiac arrest	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023) or outcome	One of the secondary objective of this study was to compare the risk of hospitalization for resuscitated cardiac arrest amoung the different ARSIs. This outcome was evaluated by the occurrence of a hospitalization for resuscitated cardiac arrest as the principal diagnosis in the French PMSI (ICD-10 code I50)
Risk of death	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023)	Another secondary objective was to evaluate the risk of death under ARSI treatment. This objective was assessed by the occurrence of death, regardless of the cause.
Risk of new registration for long term illness	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023) or outcome	Finally, a further secondary objective was to compare the risk of a new registration for long-term illness (ALD) due to cardiovascular reasons, according to the ARSI used.
Risk of hospitalization for hypertensive disease	From the beginning of the ARSI to the first date among : death, end of hormonotherapy, study endpoint date (31-12-2023) or outcome	One of the secondary objective of this study was to compare the risk of hospitalization for hypertensive disease amoung the different ARSIs. This outcome was evaluated by the occurrence of a hospitalization for hypertensive disease as the principal diagnosis in the French PMSI (ICD-10 code I10-I13; I15)

Trial Locations

Locations (1)

CHU Caen; 🇫🇷 Caen, Normandie, France