Associations between androgen deprivation therapies and adverse cardiovascular outcomes in men with prostate cancer: a population-based cohort study in England

Background: >500,000 men are living with or beyond a prostate cancer (PC) diagnosis in the United Kingdom.

Cardiovascular disease (CVD) is a leading cause of mortality in PC survivors, with wide health inequalities across ethnic and socio-economic strata of the population.

It is thought that androgen deprivation therapy (ADT), used widely in PC treatment, may be associated with raised CVD risks because of their known tendency to increase blood lipids, glycaemia, blood pressure, insulin resistance, weight gain, and changes in body fat distribution, but evidence to date is limited.

To our knowledge, no population-based study has investigated the risk of CVD outcomes associated with ADT in the UK, nor studied the predictors of CVD outcomes among PC patients. Aims: First, to quantify the burden of CVD outcomes associated with ADT in PC survivors in England. Second, to derive and validate a risk prediction score to identify men with PC at high risk of CVD associated with ADT.

Methods: We will use linked data from several databases of routinely collected electronic health records.

This will create a population-based sample of >120,000 men with PC diagnosed in 1999-2018 in England (~20% of all PC diagnoses in this period).

We will use a target trial emulation approach to quantify the absolute and relative risk of several CVD outcomes (e.g., arrythmia, heart failure, stroke) in men with PC treated with ADT and compare with those not treated with ADT.

We will investigate differences in outcomes by race and socio-economic status, and assess whether any raised risks can be explained by mediators described as adverse effects of ADT.

In the second part of this project, we will derive and validate a risk prediction tool to predict absolute CVD risks in ADT-treated patients, to help to guide treatment decisions and target monitoring and prevention during follow-up. Predictors investigated will include clinical, lifestyle and socio-demographic factors.

How the results of this research will be used: The results of this project will ensure that PC patients and their doctors make more informed treatment decisions, considering the risk-benefits of ADT; help clinicians identify patients at high risk of CVD outcomes who could be targeted for additional preventive interventions; inform on specific ethnic and/or socio-economic inequalities in CVD outcomes associated with ADT; and inform future research priorities.

This project will generate evidence to help assess whether clinical trials on safe de-escalation of ADT treatment may be warranted.