Evidence Gaps in the Era of Non–Vitamin K Oral Anticoagulants


Vitamin K antagonists (VKAs) were first introduced in the 1920s from studies on the “hemorrhagic” effect of spoiled sweet clover consumption by cattle and have evolved ever since to the cornerstone of oral anticoagulation therapy. The most commonly used VKA in the United States is warfarin, while in some European countries acenocoumarol and phenprocoumon are commonly used. VKAs exhibit their anticoagulant effect by inhibiting the vitamin K epoxide reductase complex subunit 1 in the liver. This enzyme catalyzes the post‐translational modification of vitamin K–dependent proteins. Inhibition of vitamin K epoxide reductase complex subunit 1 results in impaired synthesis of coagulation factors II (prothrombin), VII, IX, and X as well as of anticoagulant proteins C, S, and Z. The primary indications for VKA use are prophylaxis and treatment of venous thromboembolic disease (VTE, which includes deep vein thrombosis and pulmonary embolism) and of thromboembolic complications associated with atrial fibrillation (AF) and/or mechanical cardiac valves.

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Aronis KN et al. J Am Heart Assoc. 26 January, 2018;7(3). pii: e007338.