Possible Anti-atherosclerotic Action of a Direct Oral Anticoagulant

Abstract

Rupture of vulnerable atherosclerotic plaques or erosion of fibrous plaques cause thrombotic occlusion of coronary artery, leads to acute myocardial infarction or unstable angina. Both aggregation of platelets and activation of blood coagulation system play central role in thrombus formation. Blood coagulation factors, especially activated factor X and thrombin, are also involved in inflammation via activation of protease-activated receptors (PARs) expressed on vascular cells and inflammatory cells. Administration of rivaroxaban, one of direct oral anticoagulants, to apolipoprotein-E deficient (ApoE-/-) mouse attenuates progression of atherosclerotic plaque with decrease in accumulation of macrophages and expression of inflammatory cytokines. Similarly, deficiency of PAR-2 gene in bone marrow cells of ApoE-/- mouse reduces expression of inflammatory cytokines in macrophages and atherosclerotic lesion progression. A recent clinical study indicated that rivaroxaban is effective in secondary prevention of arteriosclerotic diseases when used in combination with aspirin. This effect is conceivable mainly by inhibition of thrombus formation. However, it would be possible that the anti-atherosclerotic action of rivaroxaban contributes to these favorable effects.