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.