Heart-related mortality in men on ADT: a current perspective


A newly published study in BJU International suggests (unsurprisingly) that androgen deprivation therapy (ADT) is associated with an increased risk of death among men with such cardiovascular conditions as congestive heart failure or prior heart attacks.

As many readers will be aware, the use of ADT in the treatment of advanced prostate cancer has long been associated with risk for adverse metabolic and cardiovascular effects, including increased risk for diabetes, coronary heart disease, heart attacks, and sudden cardiac death. Indeed, one of the primary reasons leading to the development and introduction of leuprolide acetate (Lupron) as a treatment for advanced prostate cancer, starting in the late in the 1970s, was that it appeared to have less risk for cardiovascular side effects than earlier forms of hormonal treatment, such as diethylstilbestrol or DES.

A research team at the Dana-Farber Cancer Institute, the Brigham and Women’s Cancer Center, and Harvard Medical School (Ziehr et al.) looked at data from > 5,000 men, all previously diagnosed with prostate cancer, who were treated between 1997 and 2006.

Here are the data reported by the Boston-based research group:

  • The total number of patients evaluated in this study was 5,077.
    • 30 percent of these patients received ADT.
    • 70 percent did not.
  • The average (median) follow-up was 4.8 years.
  • In men with no known cardiac risk factors, there was no evidence of any association between ADT and heart-related deaths.
    • Heart-related deaths had occurred in 1.08 percent of men receiving ADT after 5 years.
    • Heart-related deaths had occurred in 1.27 percent of men not receiving ADT after 5 years.
  • In men with diabetes, hypertension, or high cholesterol, there was, again, no evidence of any association between ADT and heart-related deaths.
    • Heart-related deaths had occurred in 2.09 percent of men receiving ADT after 5 years.
    • Heart-related deaths had occurred in 1.97 percent of men not receiving ADT after 5 years.
  • In men with a history of congestive heart failure or prior heart attacks, ADT was associated with a 3.3-times increased risk of heart-related deaths.
    • Heart-related deaths had occurred in 7.01 percent of men receiving ADT after 5 years.
    • Heart-related deaths had occurred in 2.01 percent of men not receiving ADT after 5 years.

The authors conclude that there is a 5 percent absolute increase in risk of death among men with  prostate cancer and a history of congestive heart failure or prior heart attacks if they are treated with ADT. They go on to suggest, therefore, that giving ADT to 20 such men could lead to the heart-related death of one of those men.

The paper’s senior author, Dr. Paul Nguyen, in a media release from the publisher of BJU International, is quoted as stating:

While [ADT] can be a lifesaving drug for men with prostate cancer and significantly increase the cure rates when used with radiation for aggressive disease, this study also raises the possibility that a small subgroup of men who have significant heart disease could experience increased cardiac death on ADT.

However, he also pointed out that the current study is a retrospective analysis. As a consequence, it’s findings need to be carefully weighed against larger controlled trials that have demonstrated the benefits of ADT:

I would still say that for men with significant heart problems, we should try to avoid ADT when it is not necessary — such as for men with low-risk disease or men receiving ADT only to shrink the prostate prior to radiation. However, for men with high-risk disease, in whom the prostate-cancer benefits of ADT likely outweigh any potential cardiac harms, ADT should be given even if they have heart problems, but the patient should be followed closely by a cardiologist to ensure that he is being carefully watched and optimized from a cardiac perspective.

The bottom line to all this is a re-emphasis on something that has been well known to experienced prostate cancer specialists for years:

  • ADT needs to be used with great caution among prostate cancer patients with significant cardiovascular problems, exemplified by such things as a history of congestive heart failure or prior heart attacks.
  • ADT should be used with appropriate awareness of the cardiovascular risks in men with high-risk and advanced forms of prostate cancer
  • ADT should be avoided if its potential benefit is unlikely to outweigh the potential risks.

 

2 Responses

  1. THE SURPRISING PLUS ASPECT OF THIS STUDY

    As a long-time patient on intermittent triple ADT (14 years), I was pleasantly surprised that no increase in risk was found for patients “with diabetes, hypertension, or high cholesterol” but perhaps (unclear) no congestive heart failure or prior heart attack.

    Of course, men in this study on ADT who were without any of these conditions were also not at higher risk. Arguably, they may be at lower risk, as the results suggest. Dr. Mark Scholz, MD, a medical oncologist who is at the forefront of prostate cancer oncology, has advanced this view. One place he has briefly described the issue is on page 101 of his book Invasion of the Prostate Snatchers, citing four studies that found either no increased risk (three studies) or a reduced risk (one study), that “offset” a single lower quality prospective study that supports the higher risk view.

    Dr. Scholz suggests a possible mechanism for reduced risk for men on ADT: the sharp reduction of testosterone results in thinner blood by decreasing the number of red blood cells, thereby allowing the blood to flow more freely, “creating less trauma to the vasculature.” He concludes: “However, the best prospective study evaluating this question shows that the net effect of [ADT] is an overall reduction in heart attacks by about 10%.” Earlier on the page, he relates the concern about heart attacks and ADT to the weight gain that frequently occurs, which tends to exacerbate diabetes. The current study seems to run counter to this line of thought.

    Dr. Charles “Snuffy” Myers, MD, another expert medical oncologist in the forefront of ADT use for prostate cancer, seems to have a less favorable view of ADT and heart trouble than does Dr. Scholz. I would love to hear these two preeminent experts discuss this important issue.

    All this noted, the use of countermeasures for this risk is another issue. I’ll address that separately.

  2. The importance of countermeasures for men with higher risk from ADT identified in this study (as well as for all the rest of us)

    Again, as a 14-year patient on intermittent triple ADT, I have been aware of various health risks with that treatment, including concerns involving diabetes and heart attacks. A number of expert medical oncologists whom I regard highly have universally championed the use of countermeasures to offset these risks for ADT patients. Diet and nutrition, exercise, and stress reduction are the three pillars of these countermeasures. These doctors have large practices, dedicated to prostate cancer, with many advanced patients referred by other doctors, and frequent use of long-term (and successful) ADT. Their extensive clinical experience has documented great success in using countermeasures to avoid or minimize the risks otherwise associated with ADT. My own experience is that I was highly successful in avoiding serious risks: my heart and lipids are in great shape (yes, total cholesterol just over 200, but an HDL over 100!); my weight was great this final round of ADT when I applied several new countermeasures; my A1c and fasting glucose were fine, etc.

    I strongly suspect that a patient with a history of congestive heart failure or prior heart attack would do very well in minimizing heart risks (and diabetes risk) if he were able to employ the recommended countermeasures.

    If this view is right, then the benefits of ADT for men who employ countermeasures will tend to strongly outweigh the risks. It follows that patients need to find advice from their doctors or elsewhere on countermeasures. That could mean finding a doctor who understands countermeasures and how to monitor the risks.

    A man on ADT who does not use countermeasures is like a soldier going into battle without body armor!

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