FROM JAMA INTERNAL MEDICINE

Warfarin, the most frequently used anticoagulant worldwide, may be associated with a lower incidence of cancer incidence across a broad range of cancer types, according to results of a large, retrospective population-based cohort study.

Compared with non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], .84; 95% CI, 0.82-0.86) and in common organ-specific cancer sites, according to the study, which included nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.

This “remarkable association” between warfarin and lower cancer incidence comes at a time when many patients are actually being transitioned away from warfarin, given its well-known dosing challenges, study authors wrote (JAMA Intern Med. 2017 Nov 6. doi: 10.1001/jamainternmed.2017.5512).

“An unintended consequence of this switch to new oral anticoagulants may be an increased incidence of cancer, which is an important consideration for public health,” Gry S. Haaland, MD , Department of Biomedicine, University of Bergen, Norway and her colleagues wrote in the report.

The study included population registry data on nearly 1.3 million Norwegians, correlated with more data from a prescription database and cancer registry in that country.

While there was no correlation between warfarin use and colon cancer, there were significantly reduced age- and sex-adjusted IRRs associated with other common organ-specific sites such as lung (.80); prostate (.69); and breast (.90), Dr. Haaland and her colleagues reported.

A subgroup analysis of the 33,313 patients (35.8%) with atrial fibrillation showed a significantly lower IRR for all cancer sites (IRR, .625) and most prevalent sites (compared with nonusers): IRR for prostate was.60; lung was.39; and the IRR for female breast cancer was .72.

The potential anticancer effects of warfarin have been suggested in various experimental cancer models. In particular, warfarin at doses not reaching anticoagulation levels has been shown to inhibits AXL receptor tyrosine kinase–dependent tumorigenesis, the authors said.

Beyond those models, there have been “conflicting conclusions” in the medical literature regarding whether warfarin protects against cancer, they added.

While some studies have shown no such association, Dr. Haaland and colleagues say they used a “stricter definition” of warfarin use that included at least 6 months of a warfarin prescription. Moreover, they only counted cancer cases that were diagnosed at least 2 years after the first prescription.

“Our data indicate that warfarin provides a possible cancer protection, a finding that may have important implications for choosing medications for patients who need anticoagulation,” the authors concluded.

However, further study is needed to better understand the mechanisms by which warfarin exerts this protective effect, they added.

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