Pharmacological Profile and Indications of Non- Vitamin K Antagonist Oral Anticoagulants: Updated Review

The non-vitamin K antagonist oral anticoagulants have been approved since 2008 for the prevention
of systemic embolism and stroke in patients with non-valvular atrial fibrillation with prior stroke,
transient ischemic attack, or CHA2DS2-VASc score ≥2. According to the latest guidelines, if CHA2DS2-
VASc score ≥2 for all male patients or if CHA2DS2-VASc score ≥3 for all female patients, oral
anticoagulants are recommended, and considering shared decision between doctor and patient.
However, they are contraindicated in patients with mechanical prosthetic valve and in patients with
moderate-to-severe mitral stenosis and atrial fibrillation. They have also been approved for prevention
and treatment of deep vein thrombosis and pulmonary embolism. Dabigatran, a direct thrombin
inhibitor, was the first to be approved, followed by the factor Xa inhibitors, rivaroxaban, apixaban, and
in 2015, edoxaban. They have advantages such as the use of fixed-dose, with infrequent drug
interaction, rapid onset of action and do not require monitoring of their anticoagulant action.
Nonetheless, they have different half-lives, the need for dose adjustment according to renal function,
weight and age of the patient. Its use in pregnant women and children or adolescents is not well
established. There are also peculiarities about the risks of bleeding, effects on coagulation tests and
specific antidotes. Through this review we discuss the pharmacokinetics and pharmacodynamics
characteristics of direct oral anticoagulants, its indications, interactions and contraindications. Analysis
of its efficacy, safety, risk-benefit ratio and costs will also be addressed.