Le 23 août 2021

AVK et syndrome myélodysplasique


A recent pathophysiological study demonstrated that Vitamin K antagonists (VKAs) compromise hematopoiesis in mice and raised the concern of a possible VKA-induced risk increase for myelodysplastic syndrome (MDS) in humans.



To clarify this concern based on real-world data, by focusing on patients with non-valvular atrial fibrillation (NVAF) and comparing VKAs to direct oral anticoagulants (DOACs).



This cohort study based on the French national healthcare database included all NVAF patients aged 18-84 years who initiated oral anticoagulants (OACs) between April 2012 and December 2016 and continued the initial treatment for at least six months. Patients with contraindications to OAC treatment, cancer history or pre-defined blood-related conditions were excluded. Follow-up started after the 6-month observation period following OAC initiation and used data up to 2019. Outcomes of interest were MDS and the composite outcome of MDS and acute myeloid leukemia (AML). A Cox proportional hazard model was applied to estimate the hazard ratio (HR), comparing VKA to DOAC initiation, and cumulative incidence curves were estimated non-parametrically. Propensity score weighting was used to adjust for numerous baseline covariates. Various additional analyses were performed.


A total of 128,248 patients was included and the mean duration from OAC initiation to end of follow-up was 4.5 years (maximum 7 years), whereby 26.9% of the patients experienced a censoring event (12.6% developed another cancer, 13.1% died and 1.3% were lost to follow-up). MDS was observed for 411 patients, corresponding to an incidence rate of 79.7 per 100,000 person-years, and MDS/AML for 479 patients. The crude and adjusted HRs of MDS when comparing VKA to DOAC were 1.45 (95% CI: 1.19-1.76) and 1.10 (0.90-1.35), respectively. For MDS/AML, they were 1.45 (1.21-1.74) and 1.11 (0.92-1.33), respectively. At 7 years after initiation, the adjusted cumulative incidence of MDS was 0.55% (0.47%-0.63%) for VKA and 0.59% (0.47%-0.72%) for DOAC. The additional analyses showed consistent results. E.g., in the per-protocol analysis, another 10.1% of the patients were censored at treatment switch from VKA to DOAC or vice versa and another 26.3% at discontinuation of OAC therapy (6 months without OAC fill) leading to crude and adjusted HRs of MDS of 1.56 (1.24-1.96) and 1.23 (0.97-1.56), respectively.



This large-scale population-based study, the first to assess the risk of MDS associated with VKA use, does not suggest an increased risk of MDS with VKA compared to DOAC in NVAF patients in the 7 years following OAC initiation.

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