Real Data on Effectiveness, Tolerability and Safety of New Oral Anticoagulant Agents: Focus on Dabigatran

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Real Data on Effectiveness, Tolerability and Safety of New Oral Anticoagulant Agents: Focus on Dabigatran Eugenio Stabile1 • Raffaele Izzo1 • Francesco Rozza1 • Maria Angela Losi1 Enrico Coscioni2 • Bruno Trimarco1



Received: 3 March 2016 / Accepted: 21 March 2016  Springer International Publishing Switzerland 2016

Abstract Vitamin K-dependent antagonists (VKAs) are the most commonly used oral anticoagulants. Non-VKA oral anticoagulants (NOACs), directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, and edoxaban) have predictable pharmacological effects and relatively few drug and food interactions compared with VKA. Among NOACs, dabigatran has been extensively tested for stroke prevention in patients with non-valvular atrial fibrillation eligible for oral anticoagulation with VKA. Dabigatran is at least as effective as warfarin at preventing stroke with advantages of less serious bleeding except for gastrointestinal bleeding, which occurs more often than with warfarin. The findings of dabigatran use in randomized trials, post market registries and specific clinical settings are discussed in this article. Keywords Anticoagulation  Atrial fibrillation  Bleeding  Stroke

& Eugenio Stabile [email protected] 1

2

Division of Cardiology, Department of Advanced Biomedical Sciences, Hypertension Research Centre, University of Napoli ‘‘Federico II’’, Naples, Italy Department of Cardiac Surgery, Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi D’aragona, Salerno, Italy

1 Introduction Vitamin K-dependent antagonists (VKAs) are the most commonly used oral anticoagulants. Although VKAs, such as warfarin, have been clinically used for more than 60 years, several challenges (i.e. bleeding complication, narrow therapeutic index, variability in patient’s response, enhanced anticoagulant effect of co-administered medications) have reported with these anticoagulants [1]. Non-VKA oral anticoagulants (NOACs), directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, and edoxaban) have predictable pharmacological effects and relatively few drug and food interactions compared with VKA. This feature allowed the drugs to be developed using fixed doses without the need for routine anticoagulation monitoring. They have a fast onset of activity (2–3 h to peak effect), which eliminates need for initial treatment with a parenteral anticoagulant in patients [2]. NOACs have been extensively tested for stroke prevention in patients with non valvular atrial fibrillation (AF) eligible for oral anticoagulation with VKA. More than 72,000 such patients have been tested in four large randomised trials. The NOACs are at least as effective as warfarin at preventing stroke, reducing the incidence of serious bleeding and of death. The findings in the four trials have been supported by observational analyses from registries. 1.1 Available Clinical Data on Dabigatran Effectiveness The randomized evaluation of long-term anticoagulation therapy (RE-LY) trial randomly assigned 18,113 patients wi