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Warfarin associated with lower risk of some cancers

Warfarin appeared to be associated with reduced cancer risk in a national European population, found an observational study.

Warfarin is a widely used anticoagulant prescribed to as many as 10% of adults in Western countries. Studies disagree on whether warfarin is associated with cancer. Any association between warfarin and cancer would be important to identify given the availability of newer non-warfarin anticoagulants.

This is the conclusion of research by Dr James B Lorens, of the University of Bergen, Norway, and co-authors.

The study included about 1.25m people born in Norway between 1924 and 1954 divided into those taking (92,942) and not taking warfarin (more than 1.1m). Individuals taking warfarin for atrial fibrillation or atrial flutter were studied as a subgroup.

Prescriptions for warfarin between 2004 and 2012 (exposure); any new cancer and most common cancers (prostate, lung, breast, colon) between 2006 and 2012 (outcome).

This is an observational study using Norwegian national registry data. In observational studies, researchers observe exposures and outcomes for patients as they occur naturally in clinical care or real life. Because researchers are not intervening for purposes of the study they cannot control natural differences that could explain study findings so they cannot prove a cause-and-effect relationship.

Results show that warfarin use was associated with lower risk of any cancer and of three of the most common cancers (prostate, lung, female breast) compared to warfarin non-use. In the subgroup of people using warfarin for atrial fibrillation or atrial flutter, cancer risk was lower at any site and in all four common sites (lung, prostate, breast, and colon).

Study limitations were outlined by the investigators: researchers did not collect information on other medications or risk factors that could influence cancer development; new cancers may actually have been cancer recurrences; and prescription of warfarin may be a marker for other health care factors that lead to cancer prevention.

In conclusion, warfarin appeared to be associated with reduced cancer risk in a national European population. The finding could have implications for choosing medications for patients who need anticoagulation but further studies to understand the mechanisms underlying any protective association are warranted.

Abstract
Importance: In cancer models, warfarin inhibits AXL receptor tyrosine kinase–dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort.
Objective: To examine the association between warfarin use and cancer incidence.
Design, Setting, and Participants: This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups—warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017.
Exposures: Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled.
Main Outcomes and Measures: Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012).
Results: Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]).
Conclusions and Relevance: 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.

Authors
Gry S Haaland, Ragnhild S Falk, Oddbjørn Straume, James B Lorens

[link url="https://media.jamanetwork.com/news-item/anticoagulant-warfarin-associated-lower-risk-cancer-incidence/"]JAMA material[/link]
[link url="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2661703"]JAMA Internal Medicine abstract[/link]

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