Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years

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.

Figure.. Adjusted Incidence Rate Ratios (IRRs) for Nonusers, Warfarin Users, and Warfarin Users With Atrial Fibrillation or Atrial Flutter (AF)

There were 1 163 783 nonusers (7 577 952 person-years), 92 942 warfarin users (430 266 person-years), and 33 313 warfarin users with AF (135 617 person-years).