title: Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives.
abstract: In recent years, several direct-acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto, Bayer HealthCare), apixaban (Eliquis, Bristol-Myers Squibb), and edoxaban (Lixiana/Savaysa, Daiichi-Sankyo). The new compounds have a predictable dose response and few drug-drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives.
authors.affiliation: Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Outes
authors.affiliation: Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.
authors.forename: Ma Luisa
authors.initials: ML
authors.lastname: Suárez-Gea
authors.affiliation: Department of Hematology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Lecumberri
authors.affiliation: Department of Clinical Pharmacology, Hospital Clínico, Madrid, Spain.|Department of Pharmacology, Universidad Complutense, Madrid, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Terleira-Fernández
authors.affiliation: Department of Clinical Pharmacology, Hospital Clínico, Madrid, Spain.|Department of Pharmacology, Universidad Complutense, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Vargas-Castrillón
mesh_terms: D000284:Administration, Oral; D062787:Drug Overdose / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D065427:Factor Xa Inhibitors; D014812:Vitamin K
keywords: anticoagulant; apixaban; dabigatran; edoxaban; rivaroxaban