Grand Rounds

Does Warfarin Protect Against Cancer?

BACKGROUND AND PURPOSE:

Warfarin is the most commonly prescribed anticoagulant, used by 5 to 10% of adults in Western countries
Warfarin depletes vitamin K pools
Most vitamin K–dependent proteins are related to clotting but there is one protein, GAS6 (growth arrest–specific 6), that is associated with immune regulatory mechanisms related to cancer
There are conflicting previous epidemiological studies as to whether warfarin inhibits tumor growth, and decreases cancer incidence
Haaland et al. (JAMA Internal Medicine, 2017) evaluated the association between warfarin use and cancer incidence in a large, unselected population-based cohort

Population-based nationwide cohort study
Study cohort: All persons born between 1924 and 1954, living in Norway between 2006 and 2012
The cohort was divided into the following groups for analysis
- Warfarin users
- Nonusers
Warfarin users were further subdivided into those taking the medication for atrial fibrillation or atrial flutter
Primary outcome: Cancer diagnosis of any type during the 7-year observation period

1,256,725 individuals were included in the study
Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years
- Women comprised 52.7% of the nonusers and 38.3% of warfarin users
Warfarin users had significantly lower age- and sex-adjusted incidence rate ratio (IRR) for cancer
- All cancer sites (IRR, 0.84; 95% CI, 0.82-0.86)
- Prevalent organ-specific sites
  - Lung, 0.80 (95% CI, 0.75-0.86)
  - Prostate, 0.69 (95% CI, 0.65-0.72)
  - breast, 0.90 (95% CI, 0.82-1.00)
There was no observed significant effect in colon cancer
In a subgroup analysis of patients with atrial fibrillation or atrial flutter, cancer IRR was lower for
- All cancer sites (IRR, 0.62; 95% CI, 0.59-0.65)
- Prevalent organ-specific 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)
  - Colon, 0.71 [95% CI, 0.63-0.81)

Warfarin appears to have broad anticancer potential
Especially in patients with arrhythmia, this study demonstrated “a remarkable association between warfarin use and lower cancer incidence”
While recognizing the benefits of the new anticoagulant agents, the authors suggest that an unintended consequence of switching away from warfarin may be increase cancer incidence

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