Cardiovascular side effects of ADT

A poster presentation given the other day at the annual meeting of the Canadian Urological Association addressed the relative cardiovascular risks of LHRH agonist and antagonist therapies.

The following information is based on a report written by Zachary Klaassen, MD, and published on the UroToday web site.

It has been suggested for a while that LHRH receptor antagonists (e.g., degarelix / Firmagon) may be associated with less risk for cardiovascular complications and side effects in treatment of men with prostate cancer than the LHRH receptor agonists (e.g., leuprolide acetate / Lupron, others).

The poster by Pinthis et al. (at McMaster University) presented in Toronto week, provided data from a small, randomized, pilot study in just an initial 66 patients. The objectives of this study were to assess (a) he impact of LHRH agonist vs antagonist on cardiovascular event rate, and (b) the potential role of follicle-stimulating hormone (FSH) in mediating ADT-induced atherosclerosis. The patients enrolled in this study all had prostate cancer, needed at least a year of androgen deprivation therapy (ADT), and all had a pre-existing cardiovascular disorder of some type.

Potential cardiovascular events were evaluated as a composite primary outcome of

  • Myocardial infarction (a heart attack)
  • Ischemic or hemorrhagic cerebrovascular events
  • Arterial embolic and thrombotic events
  • Visits to the Emergency Department or hospitalization due to ischemic heart disease (IHD), or coronary artery or peripheral vascular disease event (vascular surgery/intervention).

Here are the initial study findings:

  • 66 patients were randomized 1:1 to each arm of the trial.
  • The average (median) follow-up at time of preparation of the poster was 8.5 months.
  • There was no difference between the groups with regards to age, stage of prostate cancer, or baseline cardiovascular disease.
  • During the 8.5-months follow-up period,
    • 12 patients developed a new cardiovascular event
    • 4/12 patients were hospitalized due to IHDs
    • 1/12 patients had a myocardial infarction
    • 1/12 patients had a new ischemic cerebrovascular event
    • 10/12 patients experiencing the primary outcome were randomized to the LHRH agonist arm of the trial.
  • FSH levels decreased from pre-ADT levels by an average (median) of
    • 92 percent for men in the degarelix arm of the trial
    • 25 percent for men in the LHRH agonist arm
    • This difference is statistically significant (p = 0.0001)

It is clear from these pilot data that cardiovascular events may well develop earlier in patients with pre-existing cardiovascular disease who receive treatment with an LHRH receptor agonist compared to an LHRH antagonist … and that such events may be secondary to poor suppression of FSH. However, …

There will need to be data from a larger clinical trial (which we understand to be ongoing) to confirm these pilot data.

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