• Marcello Rattazzi, Elisabetta Faggin, Elisa Bertacco, Chiara Nardin, Leopoldo Pagliani, Mario Plebani, Francesco Cinetto, Diego Guidolin, Massimo Puato, and Paolo Pauletto.
• Department of Medicine - DIMED, University of Padova, Padova, Italy.
• Cardiovasc Ther. 2018 Aug 1; 36 (4): e12438.

IntroductionVitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification.AimsTo compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice.Results42 ApoE-/- mice fed with Western-type Diet (WTD) were randomized to treatment with warfarin (n = 14), rivaroxaban (n = 14) or control (n = 14) for 8 weeks. Histological analyses were performed to quantify the calcification of aortic valve leaflets and the development of atherosclerosis. The analyses showed a significant increase in valve calcification in mice treated with warfarin as compared to WTD alone (P = .025) or rivaroxaban (P = .005), whereas no significant differences were found between rivaroxaban and WTD (P = .35). Quantification of atherosclerosis and intimal calcification was performed on the innominate artery of the mice and no differences were found between the 3 treatments as far as atherogenesis and calcium deposition is concerned. In vitro experiments performed using bovine interstitial valve cells (VIC) showed that treatment with rivaroxaban did not prevent the osteogenic conversion of the cells but reduce the over-expression of COX-2 induced by inflammatory mediators.ConclusionWe showed that warfarin, but not rivaroxaban, could induce calcific valve degeneration in a mouse model of atherosclerosis. Both the treatments did not significantly affect the progression of atherosclerosis. Overall, these data suggest a safer profile of rivaroxaban on the risk of cardiovascular disease progression.© 2018 John Wiley & Sons Ltd.

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