Anticoagulation therapy and prostate cancer prevention

Today’s “hot news story” in the cancer world is that a very widely used drug called warfarin (often still known as Coumadin) may be able to protect people from  the risks of getting diagnosed with at least some cancers. But …

We suggest you treat this information with care!

The basis for the headlines is a set of data just published online by Haalan et al. in JAMA internal Medicine. What Haalan and his colleagues did was to use a series of detailed Norwegian databases to investigate whether there was any association between the use of warfarin (which is an anticoagulant or “blood thinner”) and the incidence of cancer in all persons born in Norway between 1924 and 1954 who were still living in Norway between January 1, 2006, and December 31, 2012.

They categorized all these people into one or other of two main groups and one subgroup:

  • Those not taking warfarin at all
  • Those taking warfarin for any reason at all
    • Those taking warfarin for atrial fibrillation or atrial flutter

They defined warfarin use as taking this prescription drug for at least 6 months and there being at least 2 years from first prescription of warfarin to any cancer diagnosis.

The primary study outcome was a cancer diagnosis of any type during the 7-year study period  from January 1, 2006, to December 31, 2012.

Here is what they found:

  • There were 1,256,725 people who qualified for inclusion in the study database.
    • 607,350 (48.3 percent) were male.
    • 649,375 (51.7 percent) were female.
    • 1,163,783 (92.6%) were non-users of warfarin.
    • 92,942 (7.4 percent) were warfarin users.
    • 132,687 (10.6 percent) got cancer during the study period.
  • The warfarin non-users tended to be younger (mean age, 63.9 ± 8.6 years) and female (613,803 = 52.7 percent).
  • The warfarin users tended to be older (mean age 70.2 ± 8.2 years) and male (57,370 = 61.7 percent).
  • Compared to the warfarin non-users, the warfarin users had a lower age- and sex-adjusted incidence rate ratio (IRR) for cancer
    • In all cancer sites (IRR = 0.84)
    • In three common, organ-specific sites
      • Lung (IRR = 0.80)
      • Prostate (IRR = 0.69)
      • Breast (IRR = 0.90)
  • There was no significant effect in colon cancer (IRR =0.99)
  • In the subgroup of patients with atrial fibrillation or atrial flutter, the IRR was lower
    • In all cancer sites (IRR = 0.62)
    • In four common, organ-specific sites
      • Lung (IRR = 0.39)
      • Prostate (IRR = 0.60)
      • Breast (IRR = 0.72)
      • Colon (IRR = 0.71)

Haalan et al. (not unreasonably) conclude that:

Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.

Specifically, if you are taking warfarin for some reason you may have a 30 percent (or higher) reduction in your risk for prostate cancer (of any type).

However, there are a number of other issues that are highly relevant to this conclusion:

  • Anticoagulants of any type should only be prescribed for those who really need this type of therapy (your sitemaster included)
  • Even if an anticoagulant of some type is needed, warfarin may not be the best or most appropriate option.
    • It has to be carefully titrated to the right dose level over time.
    • Patients on warfarin must have regular blood tests to check their warfarin levels.
    • Other forms of anticoagulant may be safer and more convenient.
  • Other generically available forms of anticoagulant (e.g., clopidigrel. also known as Plavix) may also lower risk for cancer. (We don’t know yet.)
  • This study doesn’t tell us specifically whether warfarin therapy is reducing risks for all forms of prostate cancer or only reducing risk for diagnosis with very low- and low-risk forms of prostate cancer (which may not need treatment anyway)

The hypothetical basis for this study is that, in cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and increases antitumor immune responses at doses that don’t reach the levels of those needed for  anticoagulation.  But what if it is the anticoagulative impact that is responsible for lowering risk for cancer? In that case, any form of effective anticoagulant might lower risk for cancer.

For those who need to be on warfarin therapy who don’t have cancer, this would appear to be good news. For others on other forms of anticoagulant therapy and who don’t have cancer, it may not be meaningful. And for the > 90 percent of people who aren’t on warfarin therapy, it doesn’t make any sense to start asking your doctor about this.

2 Responses

  1. Sits interestingly with the idea that some anti-coagulants might reduce Alzheimer’s risk as well. See this article in The Guardian and/or the original paper by Friberg and Rosenqvist.

  2. …and with the fact that ablation reverts stroke risk among AF patients to non-AF levels, in contrast to treatment with anticoagulants, as reported here.

    The data point in the reported paper that lung-cancer risk in a population that is taking warfarin for AF relative to a population taking it for other reasons is reduced 51% (!) has me looking for confounders rather than the anticoagulants I have in my cupboard.

    We know that silent AF has substantial incidence in a population like this (see for example here), albeit unquantified

    So a question for a study like this is: “Can it discard the hypothesis that untreated AF (and its hypothesised microclots) is a risk factor for cancer, as we know it is for stroke and apparently dementia?” If not, then the effect of the anticoagulants cannot be said not to be an artifact.

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