Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: Practical Considerations on the Choice of Agent and Dosing

Abstract

Direct or new oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have recently revolutionized the field of antithrombotic therapy for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (NVAF). Randomized controlled trials have shown that these agents have at least comparable efficacy with vitamin K antagonists along with superior safety, at least in what concerns intracranial hemorrhage. As a result, NOACs are indicated as first-line anticoagulation therapy for NVAF patients with at least one risk factor for stroke or systemic embolism. The rapid introduction, however, of NOACs in a field dominated for decades by vitamin antagonists and the variety of agents and dosing schemes may create difficulties in decision making. In the present article, we attempt to determine a practical approach to the choice of agent and dose in different clinical scenarios by considering not only the results of seminal randomized trials and post hoc analyses but also data from real-world patient populations as well as the recently available possibility of rapid NOAC reversal.

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

“…However, these recommendations are not uniform worldwide, hampering the selection of the preferable posology and the identification of DOAC suboptimal use. Indeed, the approved doses and dose adjustment criteria defined by European Medicine Agency (EMA) and Food and Drugs Administration (FDA) are summarized in Table while the recommendations reported by Health Canada regulatory agency, European Society of Cardiology and Japanese guidelines, regarding DOAC dose adjustment in patients with AF, are presented in Table . Note that Japanese guidelines mention some differences in relation to EMA and FDA, particularly related to the smaller body size, different pharmacokinetic and genetic profiles of Asian populations when compared with European or American patients.…”

“…Indeed, the approved doses and dose adjustment criteria defined by European Medicine Agency (EMA) and Food and Drugs Administration (FDA) are summarized in Table 1 16,[18][19][20][21][22][23][24][25][26][27][28][29][30][31] while the recommendations reported by Health Canada regulatory agency, European Society of Cardiology and Japanese guidelines, regarding DOAC dose adjustment in patients with AF, are presented in Table 2. 7,19,[32][33][34][35][36][37][38][39][40] Note that Japanese guidelines mention some differences in relation to EMA and FDA, particularly related to the smaller body size, different pharmacokinetic and genetic profiles of Asian populations when compared with European or American patients. All these guidelines were, hence, herein taken into consideration to assess whether DOAC dose adjustment were justified or not and, therefore infer about the impact of DOAC off-label doses on clinical outcomes of patients with AF.…”

Health-related quality of life in nonvalvular atrial fibrillation patients with controlled or uncontrolled anticoagulation status

“…These practical difficulties associated with VKAs led to the development of non-vitamin K antagonist oral anticoagulants (NOACs). NOACs maintain the benefits of anticoagulant therapy while overcoming some of the limitations of VKAs [ 16 , 17 ]. They do not require strict monitoring, have few drug and food interactions and the dosage is fixed, offering important benefits that could impact patients’ health-related QoL (HRQoL) [ 18 ].…”

New oral anticoagulants and their reversal agents

“…Its effect is fast, the median time to reversing the effect being 2.5 hours (33). Idarucizumab has been approved in Europe and is indicated in life-threatening bleedings or emergency surgery, in patients with chronic anticoagulant therapy with dabigatran (34).…”