Risk for DVT and PE as a complication of treatment with ADT


A newly published paper in Prostate Cancer and Prostatic Diseases has confirmed that there is an association between specific forms of androgen deprivation therapy (ADT) and certain types of adverse thromboembolic events.

A systematic review by Guo et al. encompassed data from five large, retrospective, cohort-based studies in which there were 256,704 patients who were not taking ADT and 170,851 patients who were.

Guo et al. showed that, based on the data from these five studies:

  • Compared to the men taking no ADT, the risk for deep vein thrombosis (DVT) was
    • Significantly increased among men taking an LHRH agonist alone (hazard ratio [HR] = 1.47; P = 0.017)
    • Significantly increased among men taking an LHRH agonist and an oral antiandrogen (HR = 2.25; P = 0.004)
    • Significantly increased among men taking an oral antiandrogen alone (HR = 1.49; P = 0.004)
    • Not significantly increased among men who had been given an orchiectomy (HR = 1.80; P = 0.079)
  • Compared to the men taking no ADT, the risk for pulmonary embolism (PE) was
    • Significantly increased among men taking an LHRH agonist alone (HR = 2.26; P < 0.001)
    • Significantly increased among men who had been given an orchiectomy (HR = 2.12; P < 0.001)
  • The associations were supported by subgroup analyses based on race and geographic location of the patients.

However. we do have to be careful how we interpret these data, because they deal with relative as opposed to absolute levels of risk.

The absolute incidence of thromboembolic events here in the US is of the order of 130 per 100,000 men per year, and that increases with age over time such that for men of 65 to 69 years of age it is more like 400 per 100,000 men per year (which is equivalent to a risk of 0.4 percent per year for a man of 65 to 69 years of age).

So, if being on ADT doubles your risk for a thromboembolic event, then this goes up from 0.4 to 0.8 percent per year for an average man of 65 to 69 years old. By comparison with all the other risks we are dealing with on a daily basis, this is still a lowish risk in absolute terms.

The takeaway here is that for any man with potential risk factors for thromboembolism — most of which are associated with a history of cardiovascular disease — the use of ADT needs to be carefully discussed with his physicians, possibly including his cardiologist, prior to initiation of ADT.

We would note that given the long history of knowledge about cardiovascular and related risks associated with the use of ADT, this new information is not exactly a big surprise. All the LHRH agonists, for example, already carry a warning about risk for cardiovascular adverse effects of treatment with these products.

 

3 Responses

  1. Thanks for reporting this updating meta-analysis, including the all-important absolute risk, which is quite low, as you note.

    I remember being cautioned about this risk way back in early 2000, shortly after starting ADT. One piece of advice was not to cross your legs, and to this day I don’t do that. I am unaware of research that supports that advice.

  2. Mild protest on the bolding of “Not” in “Not significantly increased among men who had been given an orchiectomy (HR = 1.80; P = 0.079)”. The HR is sort of median compared to the others and the P is far from random, so there is an indication but the only conclusion that can safely be drawn is that not enough men had orchiectomy for the study to be powered on that limb.

    But interesting as ever, @SM.

  3. I see your point on the HR of 1.80, a near doubling of risk, but that p value of 0.079 is much higher than researchers like to see. If a p value is not less than 0.05, the result is treated as likely due to chance. In addition to having too few men in that arm of the study, it could be that there were plenty of men but values all over the place, or a combination of rather few men and substantial variation in the values.

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