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Are LHRH Antagonists Indicated for Patients With Prostate Cancer at High Cardiovascular Risk?

By: Joseph Fanelli
Posted: Tuesday, August 30, 2022

Although there may be some advantages to using luteinizing hormone-releasing hormone (LHRH) antagonists to treat prostate cancer, such as the speed of testosterone decline and avoidance of testosterone surge, given the conflicting findings and limitations of available studies, cardiovascular risk reduction does not justify the use of these agents in patients with preexisting cardiovascular disease, according to findings in the Journal of Clinical Oncology. The optimal cardiovascular management of patients with a history of cardiovascular events should be addressed before the initiation of androgen-deprivation therapy, concluded Steven Tisseverasinghe, MD, of McGill University, Montreal, and colleagues.

“We, therefore, conclude that higher [cardiovascular] risk should be managed optimally in the [cardiovascular] sense, but this finding should not be an indication for the preferential use of LHRH antagonists in patients with prostate cancer,” the authors said.

In this meta-analysis, the authors reviewed relevant studies investigating any cardiovascular toxicity induced because of LHRH agonists. In terms of clinical studies, several have tried to determine the difference in cardiovascular events when comparing agonists and antagonists. The authors noted that although all studies in their meta-analysis had issues with short follow-up, “post hoc analysis, open-label design, and cardiovascular events were not reported as independent endpoints,” they commented.

The phase III PRONOUNCE trial was reportedly the only study designed to independently verify or adjudicate major adverse cardiovascular events because of LHRH antagonists and agonists. In the study, a statistically nonsignificant difference in major adverse cardiovascular event rates between the two arms and the lower-than-anticipated major adverse cardiovascular rate for those treated with agonists reinforced the hypothesis that cardiovascular morbidity associated with LHRH agonists may be overrated, the authors said.

“Although the quality of databases, underlying confounders, and potential biases varied between [real-world data] studies, most did not support a [cardiovascular events] benefit for patients on antagonists,” the authors concluded.

Disclosure: For full disclosures of the study authors, visit

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