Long-Term Vitamin K Antagonists and Cancer Risk: A Systematic Review and Meta-Analysis

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.

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.

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).

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.