Cardiovascular side effects and the early use of ADT — another large data set analysis


A newly published paper in BJU International has expanded our understanding of the cardiovascular risks associated with the use of androgen deprivation therapy (ADT) — most particularly in older men treated with ADT as their first-line form of therapy.

This paper by Schmid et al. is based on an analysis of data from > 50,000 men diagnosed with prostate cancer between 1992 and 2007 for whom de-identified data are available through the Surveillance, Epidemiology, and End Results (SEER) registry. What Schmid and he colleagues set out to do was to look into whether adverse cardiac events in elderly men with non-metastatic prostate cancer was in some way related to the number of doses of LHRH agonist they received over time, and on the patients’ life expectancies.

They set out to compare risk for (a)  new-onset coronary heart disease (CHD), (b) acute myocardial infarction (AMI), (c) sudden cardiac death (SCD), and (d) cardiac-related interventions, and (e) any of these four events between the men with non-metastatic prostate cancer who received ADT within 2 years of prostate cancer diagnosis and the men who did not.

To do this, they divided the ADT patients into three groups:

  • Men whose ADT was a surgical orchiectomy (Group A)
  • Men treated with an LHRH agonist who received fewer than eight monthly equivalent doses of an LHRH agonist (Group B)
  • Men treated with an LHRH agonist who received more that eight monthly equivalent doses of an LHRH agonist (Group C)

They also stratified the all patients into three categories based on their life expectancy (< 5 years, 5 to 10 years, and > 10 years).

Here is what Schmid et al. report:

  • Compared to men with non-metastatic prostate cancer who were not treated with LHRH agonists,
    • Men in Group A were not more likely to have a cardiac event of any type
    • Men in Group B were more likely to have a cardiac event of any type (hazard ratio [HR] =  1.13; P < 0.001).
    • Men in Group C were also more likely to have a cardiac event of any type (HR = 1.18; P < 0.001).
    • For the men in Group B, there was no effect on overall cardiac risk if they had a life expectancy of < 5 years (HR = 0.99; P = 0.964).
    • For the men in Group C, the effect of prolonged LHRH agonist use on risk for any cardiac event was sustained across all strata of life expectancy.
  • For the subsets of cardiac conditions,  again compared to men with non-metastatic prostate cancer who were not treated with LHRH agonists,
    • Men in Group A were
      • Not more likely to have and AMI or an SCD
      • Less likely to have cardiac-related interventions of any type (HR = 0.78; P = 0.001)
    • Men in Group B were
      • More likely to have CHD (HR =  1.13; P < 0.001).
      • Not more likely to have an AMI
      • Not more likely to have an SCD
    • Men in Group C were
      • More likely to have CHD (HR = 1.17; P < 0.001).
      • Not more likely to have an AMI
      • Not more like to have an SCD if they had a life expectancy of < 5 years
      • More likely to have an SCD if they had a life expectancy of 5 to 10 years (HR = 1.19; P = 0.003)
      • More likely to have an SCD if they had a life expectancy of > 10 years (HR = 1.16; P = 0.006)

As we have pointed out before, one does have to be cautious about how one interprets data like these from large epidemiological databases. However, Schmid and her colleagues conclude, not unreasonably, that

  • Treatment with an LHRH agonist “is associated with an increased risk of cardiac events in elderly men with localized [prostate cancer] and a decent life expectancy.”
  • “Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged life expectancy.”
  • “Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.”

According to a report on this paper on the Renal & Urology News web site, the authors also wrote (in the main text of their paper) that:

In consideration of previous reports and our study findings, it is worrying and disappointing that one in three patients still receives primary ADT as the sole treatment for localized [prostate cancer].

3 Responses

  1. I do not understand one item, and that might be due to my terminological ignorance. Does first-line here include men who got ADT as adjuvant, after say, radiotherapy?

  2. Dear George:

    I do not think so. I believe that the authors were looking exclusively at effects in men who never received any form of curative therapy (e.g., surgery or radiation therapy) and so men who had radiation therapY + adjuvant ADT would have been excluded. However, since I have only seen the abstract of the paper and not the full text, I cannot confirm that with absolute rigor.

  3. Thank you. That is what I thought, but there is no way to be sure.

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