Associations of long-term vitamin K antagonist and direct oral anticoagulant therapies with progression of coronary artery calcification: A Danish population-based study

AIMS: Vitamin K antagonists (VKAs) may promote vascular calcification through inhibition of vitamin K-dependent proteins. We aimed to examine the association between long-term anticoagulant therapy with VKA or direct oral anticoagulants (DOACs) and progression of coronary artery calcification (CAC) in a large, population-based cohort. METHODS: We included men and women (<75 years) with two non-contrast CT scans for CAC ≥4 years apart, categorized into VKA, DOAC, mixed anticoagulant, and control groups. Cumulative treatment duration was calculated from prescription data. CAC progression was analysed using zero-inflated negative binomial and multinomial logistic regression, adjusting for traditional cardiovascular risk factors, baseline CAC and follow-up time. Sensitivity analyses excluded participants predisposed to vascular mineralization (statin use, mechanical valve, renal impairment). RESULTS: 7365 participants with similar risk profile were included. VKA therapy was significantly associated with CAC progression (incidence rate ratio (IRR) = 1.004 per month of treatment (95% CI: 1.000-1.007)), showing a duration-response relationship. Long-term VKA therapy (>48months) was independently associated with higher CAC progression (IRR = 1.43 (95% CI: 1.076-1.908)), and an increased risk of having severe CAC (CAC score ≥400) at follow-up (relative risk ratio (RRR) = 1.012 per month of treatment (95% CI: 1.001-1.023)). In contrast, DOAC therapy was not associated with CAC progression. Sensitivity analyses confirmed that the association with VKA was not driven by high-risk subgroups. CONCLUSION: In this large, real-world cohort, VKA - but not DOAC - therapy was associated with accelerated, duration-dependent CAC progression. These findings suggest that choice of anticoagulant may influence CAC, yet the clinical implications remain to be determined.