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Long-Term Vitamin K Antagonists and Cancer Risk

A Systematic Review and Meta-Analysis

Shurrab, Mohammed MD, MSc*,†,‡,§; Quinn, Kieran L. MD, MSc§,∥; Kitchlu, Abhijat MD§,¶; Jackevicius, Cynthia A. BScPhm, PharmD, MSc§,#,**; Ko, Dennis T. MD, MSc§,**,††

American Journal of Clinical Oncology: September 2019 - Volume 42 - Issue 9 - p 717–724
doi: 10.1097/COC.0000000000000571
Review Articles

Objectives: Vitamin K antagonists (VKAs) remain one of the most commonly used anticoagulation therapies. The potential anticancer effect of long-term use of VKAs has been a matter of debate with conflicting results. Our goal was to perform a systematic review and meta-analysis examining the association between long-term VKAs use and cancer risk.

Methods: Systematic searches of multiple major databases were performed from inception until January 2018. We included studies of adults that compared incidence of any cancer between ≥6 months use of VKAs (long-term group) and <6 months use of VKAs or nonuse (control group). Primary outcome was all-cancer incidence and secondary outcomes were cancer-specific incidence, all-cause death and cancer-specific mortality. Hazard ratios (HRs) were pooled using a random-effects model, and individual studies were weighted using inverse variance.

Results: We identified 9 observational studies that included 1,521,408 patients. No randomized trials were identified. In comparison to control, long-term use of VKAs was associated with a significant reduction in incidence of all cancers (HR, 0.84; 95% confidence interval [CI], 0.81-0.88; P<0.001). In a prespecified subgroup analysis, long-term use of VKAs demonstrated a significant reduction in all-cancer incidence when compared with control in individuals whose indication for VKAs were venous thromboembolism (HR, 0.69; 95% CI, 0.52-0.90; P=0.007).

Conclusions: The use of long-term VKAs, for any indication, is associated with lower cancer incidence. This finding could have important clinical implications for the choice of oral anticoagulation therapies among specific patients with a higher baseline risk of cancer.

*Cardiology Department, Health Sciences North

Health Sciences North Research Institute

Northern Ontario School of Medicine, Laurentian University, Sudbury

§Institute of Health Policy, Management and Evaluation

Department of Medicine

Division of Nephrology

††Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto

**Institute for Clinical Evaluative Sciences, Toronto, ON, Canada

#Veterans Administration Greater Los Angeles Health Network, Western University of Health Sciences, Los Angeles, CA

M.S. is supported by a Fellowship Award from the Canadian Institutes of Health Research (CIHR). K.L.Q. is supported by the Eliott Phillipson Clinician Scientist Program and the Canadian Institutes of Health Research (CIHR) Vanier Scholarship. A.K. is supported by the Eliott Phillipson Clinician Scientist Program. D.T.K. is supported by a Mid-Career Investigator Award from the Heart and Stroke Foundation of Canada (HSFC), Ontario Provincial Office. C.A.J. declares no conflicts of interest.

Reprints: Dennis T. Ko, MD, MSc, Department of Medicine, Institute for Clinical Evaluative Sciences, G-106, 2075 Bayview Ave., Toronto, ON, Canada M4N 3M5. E-mail:

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