[Stroke Associated with Atrial Fibrillation and Novel Oral Anticoagulants (NOACs)]

Atrial fibrillation (AF) increases the risk of stroke and death by an embolus formed in the left atrium. Thrombus formation over the endocardium of the left atrial appendage is caused by a reduction of physiological coagulation inhibitors, such as thrombomodulin, in patients with AF. Therefore, prevention with anticoagulants is important, with warfarin treatment routinely given. Recently, novel oral anticoagulants (NOACs), a direct thrombin inhibitor (TDI), and factor Xa inhibitors (Xa-INHs) have been used for prevention in place of warfarin. However, since the half-life of NOACs is short, there are peak and trough plasma concentrations. Thus, even though thrombin formation is adequately controlled at the peak in NOAC therapy, such formation may occur at the trough, increasing the risk of thrombosis. TDI inhibits the amplification phase and Xa-INHs inhibit the propagation phase (prothrombinase complex) of the coagulation reaction, resulting in the control of thrombin bursts. In a meta-analysis of NOACs vs. warfarin treatment, the former significantly reduced stroke or systemic embolic events by 19% as compared with warfarin, mainly driven by a reduction in hemorrhagic stroke, while their administration also significantly reduced all-cause mortality by 10% and intracranial hemorrhage by 52%. Although frequent monitoring is not necessary in NOAC therapy, some clinical examinations for determining the effect and bleeding risk are required, as it was recently reported that some patients with AF who received NOAC therapy experience cerebral infarction or serious bleeding.