Can Warfarin Lower the Risk of Cancer?

A study aimed to investigate the possible association of warfarin use with reduced cancer incidence in a large Norwegian population.

Warfarin sodium is the most accepted anticoagulant globally and is prescribed to 5% to 10% of the adults for a range of indications like atrial fibrillation, prosthetic heart valves, and venous thromboembolism^{1, 2}. The antitumor potential of warfarin was demonstrated in different experimental cancer model systems^3-6. Previous epidemiological studies differ regarding the association between warfarin and cancer, with one study was suggesting a specific association with urogenital cancers⁷ and another indicating no association with cancer incidence⁸.

In a recent Norwegian study published in JAMA Internal Medicine, this nationwide cohort was divided into two groups; warfarin users and nonusers⁹. Individuals taking the anticoagulant for atrial fibrillation or atrial flutter were the subgroup of the main group of Warfarin users. Warfarin use could be defined as taking at least six months of a prescription and at least two years from the first prescription to any cancer diagnosis. The researchers used a measure known as an incidence rate ratio (IRR) to compare the rates of cancer diagnosis in people either taking or not taking warfarin. A lower incidence rate ratio indicates a lower rate of cancer.

Of the 1,256,725 people in the cohort, 10.6% had cancer, 7.4% were Warfarin users, and 92.6% were nonusers. The warfarin users were older, with a mean age of 70 years, and were predominantly men, as compared with nonusers who had a mean age of 64 years and were mostly women. Among warfarin users, and compared with nonusers, there was a significantly lower incidence rate ratio in all cancer sites and in prevalent organ-specific sites, prostate, and breast.

No significant effect in colon cancer was observed. In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR of 0.62) and in prevalent sites (lung, 0.39; prostate, 0.60; breast, 0.72; and colon, 0.71).

This important study demonstrates that warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. The research showed a lower incidence of cancer associated with warfarin, and the data indicated that warfarin gives a possible protection against cancer. This finding could have important implications for the selection of medications for patients needing anticoagulation.

Written by Dr. Swapna Aleti, Scientific Writer and Associate Professor

References:

1. Keeling D, Baglin T, Tait C, et al; British Committee for Standards in Haematology. Guidelines on oral anticoagulation with warfarin—fourth edition. Br J Haematol. 2011;154 (3):311-324.
2. Tadros R, Shakib S.Warfarin—indications, risks and drug interactions. Aust Fam Physician. 2010;39 (7):476-479.
3. Kirane A, Ludwig KF, Sorrelle N, et al. Warfarin blocks Gas6-mediated Axl activation required for pancreatic cancer epithelial plasticity and metastasis. Cancer Res. 2015;75(18):3699-3705.
4. Ryan JJ, Ketcham AS, Wexler Reduced incidence of spontaneous metastases with long-term Coumadin therapy. Ann Surg. 1968;168 (1):163-168.
5. Paolino M, Choidas A, Wallner S, et al. The E3 ligase Cbl-b and TAMreceptors regulate cancer metastasis via natural killer cells. Nature. 2014;507 (7493):508-512.
6. Williamson RC, Lyndon PJ, Tudway AJ. Effects of anticoagulation and ileal resection on the development and spread of experimental intestinal carcinomas. Br J Cancer. 1980;42(1):85-94.
7. Tagalakis V, Tamim H, Blostein M, Collet JP, Hanley JA, Kahn SR. Use of warfarin and risk of urogenital cancer: a population-based, nested case-control study. Lancet Oncol. 2007;8(5):395-402.
8. Kinnunen PT, Murtola TJ, Talala K, Taari K, Tammela TL, Auvinen A.Warfarin use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Scand J Urol. 2016; 50(6):413-419.\
9. Haaland GS, Falk RS, Straume O. Association of Warfarin Use with Lower Overall Cancer Incidence Among Patients Older Than 50 Years. JAMA Internal Medicine. 2017;177(12);1774-1780.