The Canadian journal of cardiology · 2025
Long-lasting Rivaroxaban Use Is Associated With Lower Aortic Valve Leaflet Calcification in Severe Aortic Stenosis.
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Kopytek Magdalena, Tarasiuk Jacek, Wroński Sebastian, Mazur Piotr, Ząbczyk Michał, Undas Anetta, Natorska Joanna
Аннотация
BACKGROUND: In vitro studies have demonstrated that direct oral anticoagulants (DOACs) downregulate expression of proteins involved in calcification and inflammation. In this hypothesis-testing study we evaluated whether DOAC therapy was associated with decreased valvular calcification in patients with aortic stenosis (AS) who were anticoagulated due to concomitant atrial fibrillation (AF).
METHODS: In this case-control study, 72 Caucasian patients with isolated severe AS were compared with 53 individuals with AF concomitant to severe AS who were treated with DOACs for 28.7 ± 13.8 months. Sixteen valves from AS patients on rivaroxaban (20 mg/day, AS-RIVA group) and 20 valves from age- and sex-matched non-anticoagulated patients with AS were subjected to microcomputed tomography (micro-CT) to estimate valvular calcification ex vivo. Calcium volume (CV), surface volume (SV), CV/SV ratio, and trabecular thickness (TbTh) were assessed. Valvular expression of osteopontin, nuclear factor-kappaB (NF-κB), and interleukin-6 (IL-6) were evaluated by immunostaining.
RESULTS: Micro-CT showed that patients taking rivaroxaban had a lower CV (-62.7%), lower SV (-46.2%), decreased CV/SV ratio (-35.6%), and maximal TbTh (-21.1%) when compared with patients not taking the drug (P < 0.05 for all). The duration of rivaroxaban use correlated inversely with micro-CT parameters, peak transvalvular velocity, and maximal transvalvular pressure gradient. Decreased valvular expression of osteopontin (-20.4%) and NF-κB (-26%) and 2-fold lower IL-6 fluorescence intensity were observed in the AS-RIVA group compared with the remainder (P < 0.05 for all). Moreover, osteopontin expression was inversely associated with duration of rivaroxaban use and positively with micro-CT parameters.
CONCLUSIONS: Long-term rivaroxaban use in AS patients was associated with lower aortic valve leaflet calcification, -as reflected by micro-CT parameters, and osteopontin expression, suggesting a potential impact of rivaroxaban on valvular calcification.
METHODS: In this case-control study, 72 Caucasian patients with isolated severe AS were compared with 53 individuals with AF concomitant to severe AS who were treated with DOACs for 28.7 ± 13.8 months. Sixteen valves from AS patients on rivaroxaban (20 mg/day, AS-RIVA group) and 20 valves from age- and sex-matched non-anticoagulated patients with AS were subjected to microcomputed tomography (micro-CT) to estimate valvular calcification ex vivo. Calcium volume (CV), surface volume (SV), CV/SV ratio, and trabecular thickness (TbTh) were assessed. Valvular expression of osteopontin, nuclear factor-kappaB (NF-κB), and interleukin-6 (IL-6) were evaluated by immunostaining.
RESULTS: Micro-CT showed that patients taking rivaroxaban had a lower CV (-62.7%), lower SV (-46.2%), decreased CV/SV ratio (-35.6%), and maximal TbTh (-21.1%) when compared with patients not taking the drug (P < 0.05 for all). The duration of rivaroxaban use correlated inversely with micro-CT parameters, peak transvalvular velocity, and maximal transvalvular pressure gradient. Decreased valvular expression of osteopontin (-20.4%) and NF-κB (-26%) and 2-fold lower IL-6 fluorescence intensity were observed in the AS-RIVA group compared with the remainder (P < 0.05 for all). Moreover, osteopontin expression was inversely associated with duration of rivaroxaban use and positively with micro-CT parameters.
CONCLUSIONS: Long-term rivaroxaban use in AS patients was associated with lower aortic valve leaflet calcification, -as reflected by micro-CT parameters, and osteopontin expression, suggesting a potential impact of rivaroxaban on valvular calcification.