Journal Article

Direct oral anticoagulants: evidence and unresolved issues

Chan, Noel, Eikelboom, John W, Sobieraj-Teague, Magdalena

2020

Overview

Currently licenced direct oral anticoagulants selectively target thrombin (eg, dabigatran) or coagulation factor Xa (eg, apixaban, betrixaban, edoxaban, and rivaroxaban). Designed to be given in fixed doses without routine monitoring, direct oral anticoagulants have a lower propensity for food and drug interactions than do vitamin K antagonists, and in randomised controlled trials involving around 250 000 patients, they were at least as effective for prevention and treatment of thrombosis and were associated with a lower risk of life-threatening bleeding. The absolute benefits of direct oral anticoagulants over vitamin K antagonists are modest; however, guidelines recommend them in preference to vitamin K antagonists for most indications because of their ease of use and superior safety. The greatest benefits of direct oral anticoagulants are likely to be in patients who were previously deemed unsuitable for vitamin K antagonist therapy. The emergence of generic preparations is expected to further increase the uptake of direct oral anticoagulants, particularly in countries where they are currently not widely used because of cost. Direct oral anticoagulants are contraindicated in patients with mechanical heart valves and should be used with caution or avoided in patients with advanced kidney or liver disease. In this Therapeutics paper, we review the pharmacology of direct oral anticoagulants, summarise the evidence that led to their approval and incorporation into treatment guidelines, and explore key unresolved issues. We also briefly discuss future perspectives for the development of oral anticoagulants.

• Publisher: Elsevier Ltd,Elsevier B.V,Elsevier Limited
• Subject: Administration, Oral / Antagonists / Anticoagulants / Anticoagulants (Medicine) / Anticoagulants - pharmacology / Anticoagulants - therapeutic use / Atherosclerosis / Bleeding / Blood clot / Cancer therapies / Cardiac arrhythmia / Cardiac patients / Cardiovascular agents / Clinical medicine / Clinical trials / Coagulation / Coagulation factor Xa / Creatinine / Dabigatran - pharmacology / Dabigatran - therapeutic use / Drug dosages / Drug interactions / Factor Xa Inhibitors - pharmacology / Factor Xa Inhibitors - therapeutic use / FDA approval / Food-drug interactions / Guidelines / Heart valves / Hemorrhage - complications / Humans / Liver / Liver diseases / Pharmacology / Phylloquinone / Prevention / Pyrazoles - pharmacology / Pyrazoles - therapeutic use / Pyridines - pharmacology / Pyridines - therapeutic use / Pyridones - pharmacology / Pyridones - therapeutic use / Research institutes / Rivaroxaban - pharmacology / Rivaroxaban - therapeutic use / Stroke / Surgery / Thiazoles - pharmacology / Thiazoles - therapeutic use / Thrombin / Thromboembolism / Thrombosis / Venous Thromboembolism - prevention & control / Vitamin K