<p>The risk of prostate cancer significantly increases with age, so many patients with prostate cancer are older and have comorbidities that are common with older age. Cardiovascular disease (CVD) is a common comorbidity, and the addition of ADT and ARPI therapy in these patients may come with additional considerations regarding CV risk and optimal management.</p>

Understanding a patient’s CV health is important for 2 major reasons. One is to be aware of their risk for noncancer morbidity and mortality. If an older patient is frail and has severe CVD, that should impact your thinking about optimal systemic treatment for their prostate cancer. The other reason is to consider the impact that treatment could have on the patient’s CVD risk. If a patient has a shorter life expectancy because of CVD, that is going to impact decisions about drugs designed to improve overall survival. In addition, separate from overall survival, we also need to think about the potential for CV morbidity in all of our patients, but particularly in those who have preexisting CVD.

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Although ADT has been associated with an increased risk of CV events, the effect size is probably modest. However, sometimes the risk is discussed as though CV events are a certain and inevitable consequence of treatment with ADT. The risk should not be diminished, but it also should not be exaggerated because it could scare clinicians or patients out of using appropriate therapy.

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GnRH antagonists appear to have a lower risk for CV events than GnRH agonists. Large, primarily population-based studies have suggested that GnRH agonists increase CVD risk, although the supporting evidence is relatively weak. Studies comparing the efficacy of GnRH agonists and antagonists have also reported fewer CV events among those receiving GnRH antagonists.

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So, I like using GnRH antagonists for patients with prostate cancer who have a particularly serious CVD risk because of 2 main benefits of therapy. First, GnRH antagonists may pose less CV risk to the patient. Second, they have a rapid on-and-off effect. The rapid off effect is very attractive in cases where you might like to quickly discontinue a patient’s treatment. After discontinuing a GnRH agonist, testosterone recovery is typically much more delayed compared with testosterone recovery after the cessation of a GnRH antagonist. However, the rapid on-and-off effects can raise concerns for orally administered GnRH antagonists in patients who you worry might have issues with compliance. Therefore, I find it very important to monitor serum testosterone in those who are taking an oral GnRH antagonist to confirm compliance with the recommended treatment.

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In terms of adding ARPIs to ADT, abiraterone can lead to hypertension, hypokalemia, arrhythmias, and edema. Hypertension requires close monitoring, and some patients will require the initiation or an increased dose of an antihypertensive medication or the addition of a second antihypertensive medication to address it. Abiraterone is not suitable for patients who have preexisting congestive heart failure or a reduced ejection fraction. The other ARPIs seem to fairly consistently increase the risk of hypertension too, and some evidence suggests that any ARPI may increase the risk of CV events to some degree. So, you want to be sure that you are using these drugs for the right reasons and to whatever extent possible to reduce the individual’s risk for harm.