The overall risk for major adverse cardiovascular events (MACE) in men with prostate cancer treated with androgen deprivation therapy (ADT) may be lower than previously assumed, with a rate of 1% during the first year following ADT initiation and 3.7% during the first 4 years, according to new real-world data presented at the Society of Urologic Oncology 22nd Annual Meeting.

“This study is what happens in real life,” said lead author Przemyslaw W. Twardowski, MD, from the departments of medical oncology and urologic oncology at Saint John’s Cancer Institute in Santa Monica, California. “The findings are somewhat more optimistic than what might be expected.” 

Men with prostate cancer are known to be at an increased risk for cardiovascular (CV) events. A previous study published in BJU International suggested CV event rates over a 10-year period were 17% to 27% among men treated with ADT. The men were treated between 1995 and 2009.

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The new study analyzed the US electronic medical records of 45,059 men with prostate cancer receiving a luteinizing hormone releasing hormone (LHRH) agonist and antagonist injections. The team examined the rate of MACE within 6 months and 1 year of ADT initiation. The database contained 965 documented MACE events.

MACE was defined as myocardial infarction, stroke, and death from any cause. The first MACE experience was used for analysis, and events occurring on the day of ADT initiation were excluded. Rates of MACE were calculated for the entire cohort and also for race. Only men with 6 months and 1 year data points were included in the general analysis.

Within each analysis set, 82% of men were White, 16% were Black, and 2% were Asian. The rate of MACE within 6 months of ADT initiation was 0.5% for the entire cohort, but it varied by race or ethnicity. It was 0.5% for White men, 0.2% for Black men and 0.0% for Asian men.

The rate of MACE within 1 year of ADT initiation was 0.8% for the entire cohort (0.9% for White men, 0.4% for Black men, and 0.3% for Asian men). The risk of MACE was significantly higher in White men compared with Black men for both time periods. “It was against what was expected. It was surprising to me that White men had high rates. I think we need to look at more risk factors in a more granular way,” Dr Twardowski said.

The reasons why race is a predictor of MACE risk is unknown. Dr Twardowski said future studies need to look at more than just MACE and factor in comorbidities. “The risk may not be as great as we thought,”Dr Twardowski said. “I think the findings are provocative, but these retrospective studies have some limitations, such as how accurate these databases really are.”

Christopher Saigal, MD, MPH, professor and vice chair of urology at the David Geffen School of Medicine at the University of California in Los Angeles, said this study will need to be validated because it is uncertain how accurately this one individual health system captured all of the MACE events in this patient population. “It is possible that events occurred at nearby hospitals and were not recorded. The [study] abstract does not make clear how underlying MACE risk factors were accounted for in the calculation of event rates,” Dr Saigal said.

Anthony V. D’Amico, MD, PhD, chief of the Division of Genitourinary Radiation Oncology at the Dana-Farber Cancer Institute and professor of radiation oncology at Harvard Medical School in Massachusetts, said the MACE rates found in the current study are most likely on target as a consequence of improved medical management and new therapeutic agents. “I think the rates are lower because of increased awareness by treating physicians of the potential CV risks of ADT and as a result are proactive in assessing CV risk before initiating ADT and correcting any CV issues,” Dr D’Amico said. “There also could be a shift toward LHRH antagonists, which have a lower risk of MACE.”

Eiman Jahangir, MD, MPH, associate professor of medicine at Vanderbilt University in Nashville, Tennessee, said the findings are clinically relevant because they add to the current body of knowledge about how the shift toward LHRH antagonists may be affecting MACE risk factors. The new findings, however, will need to be replicated in prospective studies, he said. Regardless, all men receiving ADT should be optimized from a cardiovascular risk standpoint, Dr Jahangir said. “Furthermore, as new ADTs are introduced, monitoring for cardiovascular effects is important. There is variability in what each treatment can cause.”


Twardowski PW, Boldt-Houle DM, Atkinson SN. Comparison of risk of major cardiovascular events with androgen deprivation therapy by race using real-world data. Presented at the Society of Urologic Oncology 22nd annual meeting, December 1-3, 2021. Poster 221.