Direct oral anticoagulants: key considerations for use to prevent stroke in patients with nonvalvular atrial fibrillation

: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher dis-ability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS 2 and CHA 2 DS 2 -VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; eg, warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (eg, those with renal impairment) and other specific clinical situations. 2 of the following criteria: age $ 80 years, body weight # 60 kg, or a serum creatinine level $ 1.5 mg/dL; b doses of edoxaban were halved if the patients had CrCl of 30–50 mL/min; body weight # 60 kg; or concomitant use of verapamil, quinidine, or dronedarone at randomization or during the study; c a reduced dose of rivaroxaban (15 mg od) was used in patients with moderate renal impairment (CrCl 30–49 mL/min); d defined according to the criteria of the ISTH as clinically overt bleeding accompanied by a decrease in hemoglobin level of $ 2 g/dL over a 24-hour period or transfusion of $ 2 units of whole blood or red cells, occurring at a critical site or resulting in death; e defined as a reduction in hemoglobin level of $ 20 g/L, transfusion of $ 2 units of blood, or symptomatic bleeding in a critical area or organ; f defined as clinically overt bleeding associated with fatal outcome, involving a critical site, or clinically overt bleeding associated with a fall in hemoglobin concentration of $ 2 g/dL adjusted for blood transfusions or a fall in hematocrit of $ 6.0% adjusted for blood transfusions; g defined as clinically overt bleeding associated with fatal outcome, involving a critical site, or clinically overt bleeding associated with a fall in hemoglobin concentration of $ 2 g/dL, or leading to transfusion of $ 2 units of packed red blood cells or whole blood; h as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician (visit or telephone call), temporary cessation (ie, by delaying the next administration) of study drug, or impairment of daily activities.