ADT and the Risk of Major Adverse Cardiovascular Events - Episode 7

Real-World Patients With High Risk of MACEs


Dipti Gupta, MD, MPH: Randomized controlled trials did not actually include high cardiac risk patients, the patients that we just talked about, the real-world patient who has hypertension, who has diabetes, who has established coronary disease. As such, they’re not even recruiting these patients in the clinical trials, nor are they studying the cardiovascular endpoints as a primary endpoint. When they go back and look at this predominantly healthy population for whom cardiovascular endpoints are actually not the primary endpoints, they fail to show an association or a causation between cardiovascular risk and therapies for prostate cancer. On the other hand, observational large scale, thousands of patients in observational trials over the past 2 decades have consistently showed increased cardiovascular risk in these patients that have been getting androgen deprivation therapy [ADT].

And as we saw with metabolic aberrations, that they don’t actually take a long time to develop after we start androgen deprivation, we see the same effect with cardiovascular risk as well. Meaning it doesn’t really take years to develop increased cardiovascular risk. It actually happens fairly soon after starting therapy. There was an elegant observational study that was done in a Swedish cohort, published a couple years ago, in over 41,000 patients with prostate cancer, which showed that the cardiovascular risk was 21% higher in patients on GnRH [gonadotropin-releasing hormone] agonists compared with a cancer-free cohort.

In this patient population, they also showed that the cardiovascular risk was highest in the 6 months after starting ADT, and it was highest in patients who had had 2 or more adverse cardiovascular events in the year preceding the ADT treatment. So the higher risk your patient is, the more likelihood that they will develop 1 of these cardiovascular complications soon after they go on androgen deprivation therapy.

This risk is not confined to cardiovascular disease. This risk with androgen deprivation actually extends to other vascular beds. There have been studies that have been published in the early 2000s that have shown in very robust cohorts, one was a UK-based cohort of over 22,000 followed for about 4 years of prostate cancer that showed an 18% increase in CVA [cerebrovascular accident] and TIA [transient ischemic attack] in these patients on GnRH agonists. A year later, another study, which was a US-based population study that was published, showed almost a 15% to 20% increase in venous thromboembolism as well as peripheral arterial disease in this population.

Transcript Edited for Clarity