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

METHODS:

• 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

RESULTS:

• 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)

CONCLUSION:

• 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

Learn More – Primary Sources:

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

Related ObG Topics:

Abnormal Vaginal Bleeding and Oral Anticoagulants for DVT – Results from the AMPLIFY trial

Can Genotype-Guided Dosing Decrease Warfarin Complications?