Vitamin K antagonists (VKAs) may be associated with a reduced risk of severe exacerbations and death in patients with chronic obstructive pulmonary disease (COPD), according to new nationwide cohort data from Denmark. The findings challenge assumptions about the potential harms of vitamin K antagonism in lung disease and raise questions about the biological role of vitamin K in COPD progression.
Exploring the Role of Vitamin K in COPD Progression
Vitamin K has been hypothesised to exert a lung-protective effect through activation of matrix Gla protein, which inhibits tissue calcification. In theory, treatment with VKAs, commonly prescribed anticoagulants for atrial fibrillation, could impair this pathway, potentially increasing the risk of acute exacerbations of COPD (AE-COPD) and mortality. To test this hypothesis, researchers compared outcomes in COPD patients treated with VKAs versus those receiving direct oral anticoagulants (DOACs), which do not interfere with vitamin K.
Using Danish nationwide health registers, the investigators conducted an observational cohort study including 7,091 patients with COPD and atrial fibrillation or flutter. Of these, 3,455 (48.7%) were treated with VKAs, while the remainder received DOACs. Patients were followed for one year to assess a composite outcome of hospitalisation due to severe AE-COPD or all-cause mortality.
During follow-up, 1,955 patients reached the primary endpoint, including 820 in the VKA-treated group. In adjusted Cox proportional hazards models accounting for established confounders, VKA treatment was associated with a significantly lower risk of AE-COPD hospitalisation or death compared with DOAC therapy (adjusted hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.78–0.98; p=0.024).
However, the robustness of this association was tempered by sensitivity analyses. In a complete-case analysis, the protective association persisted but did not reach statistical significance (adjusted HR 0.88; 95% CI 0.76–1.01). Similarly, inverse probability of treatment weighting yielded an HR of 0.85 (95% CI 0.72–1.01), again falling short of statistical significance.
Implications for Future COPD Research and Clinical Trials
The authors note that, contrary to the initial hypothesis, VKA treatment was not associated with worse outcomes in COPD patients and may even confer a modest protective effect compared with DOACs. While the observational design precludes causal inference, the findings suggest that concerns about VKA-related harm in COPD may be overstated.
Further mechanistic and prospective studies are needed to clarify the role of vitamin K pathways in lung disease and to determine whether anticoagulant choice meaningfully influences COPD outcomes in clinical practice.
Reference
Gunderson BVV et al. COPD and vitamin K antagonism: a cohort study of 1-year all-cause mortality and risk of hospitalisation due to a severe exacerbation. BMJ Open Respir Res. 2026;13:e003814.
