Low Dose Rivaroxaban for the Management of Atherosclerotic Cardiovascular Disease

Atherosclerotic cardiovascular disease is characterized by some risk of major adverse events despite the availability of effective medical therapies for secondary prevention. There is emerging evidence suggesting that thrombin partly contributes to this residual risk. In fact, thrombin (i.e., activated coagulation factor II) triggers not only the conversion of fibrinogen to fibrin but also platelet activation and various pathways responsible for pro-atherogenic and/or pro-inflammatory effects through interaction with protease activated receptors. To reduce the risk associated with thrombin activation, oral anticoagulants antagonists of vitamin K showed promise, but were associated with unacceptable bleeding rates. Direct oral anticoagulants targeting the activated factors X and II carry a lower risk of bleeding than vitamin K antagonists. Rivaroxaban, a direct inhibitor of activated factor X approved at the dose of 20 mg once daily for the prevention of thromboembolic events, has been also investigated at a reduced dose of 2.5 mg twice daily in several alternative scenarios of atherosclerotic cardiovascular disease, in combination with standard of care. Current guidelines recommend that low-dose rivaroxaban is given in an adjunct to standard therapy to patients with stable atherosclerosis and acute coronary syndromes at low bleeding risk. Several studies are underway to evaluate its putative benefits in other clinical settings. Atherosclerotic cardiovascular disease is burdened by some risk of adverse clinical events complicating its course. Thrombin is the most potent endogenous platelet agonist capable of activating platelets via protease activated receptors. These receptors trigger various signaling pathways responsible for unfavorable cardiovascular effects (i.e., atherogenesis, inflammation). Thrombin activation persists for several months after an acute event. Low-dose rivaroxaban is recommended as a secondary prevention strategy by current guidelines for patients with stable atherosclerosis and acute coronary syndromes at low bleeding risk. Several trials are underway to evaluate the putative benefits of low-dose rivaroxaban in other clinical settings, including stroke and chronic kidney disease.