New Oral Anticoagulants in Non-Valvular Atrial Fibrillation
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REVIEW ARTICLE
New Oral Anticoagulants in Non-Valvular Atrial Fibrillation Pietro Francia • Carmen Adduci • Daria Santini Beatrice Musumeci • Giuliano Tocci
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Received: 25 January 2013 / Accepted: 4 March 2013 / Published online: 8 May 2013 Ó Springer International Publishing Switzerland 2013
Abstract Atrial fibrillation (AF) is associated with an increased risk of embolic stroke. Dose-adjusted vitamin K antagonists (VKAs) to a target international normalized ratio (INR) range of 2.0–3.0 reduce the risk of ischemic stroke and are currently recommended in all patients with AF at moderate-high risk for stroke or systemic embolism. However, VKAs have several drawbacks, including unpredictable anticoagulant response, food and drug interactions, need for regular laboratory monitoring and dose adjustment. These limitations prompted the introduction of new oral anticoagulants (NOA) that target thrombin and factor Xa, key-enzymes in the coagulation pathway. NOA have predictable pharmacodynamics, allowing fixed dosing without the need of laboratory monitoring, and have few drug and food interactions. The present review focuses on pharmacological properties, safety, and appropriate clinical use of dabigatran, rivaroxaban and apixaban. Keywords Oral anticoagulants Atrial fibrillation Apixaban Rivaroxaban Dabigatran
1 Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia, occurring in 1.5–2 % of the general population and up to 5–15 % in patients aged C80 years [1]. Although
commonly associated with comorbidities [2], AF also occurs in subjects without structural heart disease or left atrial remodelling [3]. AF is associated with an increased risk of embolic stroke, a costly disease from human, family and societal perspectives. Dose-adjusted vitamin K antagonists (VKAs) to a target international normalized ratio (INR) range of 2.0–3.0 lower the risk of stroke compared to placebo or antiplatelet therapy, with acceptable rates of bleeding complications [4]. Therefore, VKAs are currently recommended in all AF patients at moderate-high risk for stroke or systemic embolism [1]. Although effective, VKAs have several drawbacks, including unpredictable anticoagulant response, food and drug interactions, and the need for regular laboratory monitoring [5]. These limitations prompted the introduction of new oral anticoagulants (NOA) that target thrombin and factor Xa, key-enzymes in the coagulation pathway. NOA have predictable pharmacodynamics, allowing fixed dosing without the need of laboratory monitoring, and have few drug and food interactions. The present review focuses on pharmacological properties, safety profile, and appropriate clinical use of dabigatran, rivaroxaban and apixaban, the three NOA that completed phase III clinical trials and were approved by the US Food and Drug Administration (FDA) and the European Medical Agency (EMA).
2 Pharmacology P. Francia (&) C. Adduci D. Santini B. Musumeci G. Tocci Division of Cardiology, Department of Clinical and Molecular Medicine, University
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