Association of Vitamin K and Non-Vitamin K Oral Anticoagulant Use and Cancer Incidence in Atrial Fibrillation Patients

Abstract

The association between the use of vitamin K antagonists (VKAs) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKAs or direct oral anticoagulants (DOACs) and the incidence of cancer in a large cohort of patients with atrial fibrillation (AF) by means of a population-based, propensity-weighted cohort study using population-wide databases including patients diagnosed with nonvalvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumors (lung, colon, prostate, bladder, and breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1,000 person-year in the DOAC cohort vs. 14.55 in the VKA cohort (adjusted hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.02-1.32). In secondary outcomes, no differences were found for specific types of cancer, such as lung (HR: 1.28, CI: 0.89-1.83), colon (HR: 0.84, CI: 0.62-1.13), prostate (HR: 1.40, CI: 0.94-2.10), bladder (HR: 1.07, CI: 0.76-1.52), and breast (HR: 1.05, CI: 0.66-1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68, 95% CI: 0.48-0.96). Our results do not confirm a chemoprotective effect of VKA when compared with DOAC in a large, real-world cohort of patients with NVAF followed for up to 5 years.

Figure 1

Study population. DOAC, direct oral anticoagulant; NVAF, nonvalvular atrial fibrillation; OAC, oral anticoagulant; VKA, vitamin K antagonist; VTE, venous thromboembolism.

Figure 2

Cancer incidence in VKA initiators vs. DOAC initiators. Adjusted hazard ratios. CI, confidence interval; HR, hazard ratio; NOAC, nonvalvular atrial fibrillation; VKA, vitamin K antagonist.

Figure 3

Kaplan Meier survival curves for the primary and secondary end point over the 5‐year observation period. NOAC, nonvalvular atrial fibrillation; VKA, vitamin K antagonist. [Colour figure can be viewed at wileyonlinelibrary.com]