REVIEW: New Antithrombotics for Atrial Fibrillation

Abstract

SUMMARY Atrial fibrillation (AF) is the most commonly occurring arrhythmia, and is a condition of both significant clinical and economic importance. An antithrombotic agent is considered mandatory as part of the management in most patients with AF. It has been conclusively demonstrated that long‐term anticoagulation therapy can significantly reduce the risk of stroke in patients with nonvalvular AF. While vitamin K antagonists (VKAs) such as warfarin are highly effective, they possess numerous limitations that curtail their use, or make their use challenging for clinicians and patients. A new generation of anticoagulants are being investigated in phase III clinical trials in patients with AF. One or more of these agents have the potential to either replace or act as alternatives to VKA therapy in AF. This group includes the direct thrombin inhibitor, dabigatran, the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, and finally, the vitamin K analogue, tecarfarin. Additional agents are being developed in phase I or II clinical trials. The direct thrombin and factor Xa inhibitors are generally small, synthetic molecules with predictable pharmacokinetics, a predictable pharmacodynamic effect, few drug interactions and do not require routine therapeutic drug monitoring. These new anticoagulants may well represent a new era in anticoagulation. However, they do possess their own limitations and will present new challenges for clinicians.

Cardioembolic stroke: a variety of causes and current approaches to its prevention

“…Из-за «неудобства» варфарина врачи предпочитают ему АСК, использование которой пра-ктически не требует лабораторного контроля. Однако следу-ет помнить, что применение АСК и ее комбинации с клопи-догрелем для профилактики эмболических осложнений при ФП сопровождалось сопоставимым с АВК риском геморра-гических событий, но значительно уступало по эффективно-сти предупреждения инсульта и системных эмболий [32][33][34]. Другой альтернативой предотвращения инсульта при ФП может служить чрескожная имплантация устройства для ок-клюзии ушка левого предсердия.…”

The Future of Anticoagulant Therapy

“…Major advances in the development of oral anticoagulants have resulted in considerable progress towards the goal of safe and effective oral anticoagulants that do not require frequent monitoring or dose adjustment, and have minimal food/drug interactions as highlighted recently in several reports [1][2][3][4][5][6][7] and summarized in recent reviews in Cardiovascular Therapeutics and other journals [1][2][3][4]. Indirect inhibitors of factor Xa and factor IIa such as lowmolecular weight heparin (LMWH) and the pentasaccharide fondaparinux represent improvements over traditional drugs, such as unfractionated heparin, for acute treatment of VTE, constituting a more targeted anticoagulant approach, with predictable pharmacokinetic profiles, and no requirement for monitoring [6,7].…”

“…The oral direct thrombin inhibitor ximelagatran was withdrawn from the world market due to safety concerns. Newer anticoagulant drugs such as oral direct thrombin inhibitors (dabigatran), oral direct factor Xa inhibitors (rivaroxaban, apixaban, and several others) are being introduced into the European and Canadian markets and have the potential to greatly expand oral antithrombotics for both acute and longterm treatment of VTE, and for the prevention of stroke in atrial fibrillation patients [1][2][3][4][5][6][7][8][9]. See Figure 1 for historical progression in anticoagulation and Figure 2 for the structure of the first oral direct anti-Xa and the first direct anti-IIa.…”

Oral anticoagulants and clinical decision making for stroke prevention in non-valvular atrial fibrillation for nurse practitioners

“…Direct thrombin inhibitors bind to and inhibit both soluble and clot bound thrombin , which is the most potent platelet agonist (Bereznicki & Peterson, 2010;Mahtani et al, 2012). This has the advantage of preventing feedback activation of factors V, VIII, and XI (Mahtani et al).…”

“…They are able to reversibly inhibit FXa when it is present in the prothrombinase complex, as well as when it is "free" (Bereznicki & Peterson, 2010). Factor Xa is an attractive target for anticoagulation because it acts as a convergence point of both the extrinsic and intrinsic coagulation pathway (Mann, Brummel, & Butenas, cited in Maan , et al, 2012).…”