Abstract
Non-vitamin K oral anticoagulants (NOACs) are the first choice for prophylaxis of cardioembolism in patients with non-valvular atrial fibrillation (AF) who are anticoagulant-naïve, as well as the preferable anticoagulation strategy in those who are on vitamin K antagonists (VKAs), but with a low time in therapeutic range (TTR). Nonetheless, there are many good reasons to consider switching from VKAs to NOACs also when TTR is >70%. From the pharmacological standpoint, anticoagulation with VKAs may remain erratic even in those patients who have high TTR values, owing to the mode of action of this drug class. Furthermore, experimental data suggest that, unlike VKAs, NOACs favorably modulate the effects of factor Xa and thrombin in the cardiovascular system through the protease-activated receptor family. Clinically, the most striking advantage provided by NOACs over VKAs, irrespective of the TTR, is the substantially lower risk of intracranial hemorrhage. NOACs have also been associated with less deterioration of renal function as compared with VKAs and may confer protection against cardiovascular events not strictly related to AF, especially the acute complications of peripheral artery disease. In this narrative review, we discuss the evidence according to which it is warranted to systematically substitute NOACs for VKAs for the prevention of AF-related stroke and systemic embolism.
Highlights
Non-valvular atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice; worldwide, 43.6 million individuals had prevalent AF or atrial flutter in 2016 [1].The currently estimated prevalence of AF in adults is 2–4% [1], and a constant increase is expected, with extended longevity in the general population and intensifying search for undiagnosed AF [2]
Reasons why Non-vitamin K oral anticoagulants (NOACs) lead to a lower rate of intracranial hemorrhage (ICH) are still largely speculative, but at least in part appear to be due to the lack of interference by NOACs with the tissue factor-FXa pathway, which is an important factor protecting from cerebral bleeding, and curtailed by the decreased concentrations of FVIIa in the plasma of vitamin K antagonists (VKAs)-treated patients [68] (Figure 1)
It was recently reported that FXa and protease-activated receptors (PARs)-2 exacerbate, and edoxaban ameliorates, diabetic nephropathy through the modulation of inflammation [82]. Data from both randomized controlled trials (RCTs) and real life provide a piece of evidence that helps clinicians in weighing the benefits and risk of NOACs versus warfarin, since at least some NOACs are associated with less nephrotoxicity
Summary
Non-valvular atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice; worldwide, 43.6 million individuals had prevalent AF or atrial flutter in 2016 [1]. VKA therapy has several limitations, including the need of overlapping heparin until the targeted effect is achieved due to its slow onset/offset of action, significant food and drug interactions, narrow therapeutic window, and unpredictable anticoagulant effect, making it difficult to implement this type of OAC in routine clinical practice [11]. NOACs were introduced to circumvent the limitations associated with VKA therapy in clinical practice, since they have a more predictable response, rapid onset/offset of action, no interaction with food, and fewer drug–drug interactions. These pharmacokinetic properties enable the administration of fixed doses without the need for routine coagulation monitoring, thereby simplifying treatment. Since VKA stability is difficult to predict, patients who have done well taking VKAs should not deter physicians from recommending the substitution of a target-specific anticoagulant (NOAC)
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