Straight to the heart: Pleiotropic antiarrhythmic actions of oral anticoagulants

Abstract

Mechanistic understanding of atrial fibrillation (AF) pathophysiology and the complex bidirectional relationship with thromboembolic risk remains limited. Oral anticoagulation is a mainstay of AF management. An emerging concept is that anticoagulants may themselves have potential pleiotropic disease-modifying effects. We here review the available evidence for hemostasis-independent actions of the oral anticoagulants on electrical and structural remodeling, and the inflammatory component of the vulnerable substrate.

Anticoagulant and antiarrhythmic effects of heparin in the treatment of COVID‐19 patients

“…6 The physiological purpose of this extravascular fibrin is possibly to serve as a matrix on which inflammatory cells can attach and function. 7 This extravascular fibrin breakdown could also explain the marked increase in D-dimers noted in patients with malignancies even in the absence of clots in the circulation. 8 How is the extravascular fibrinolysis relevant to COVID-19?…”

“…We would also like to add that, while a direct anticoagulant effect is likely crucial to the therapeutic effect of heparin, it also has antiarrhythmic properties [6,7] that could show promise in the treatment of COVID-19, in which cardiac arrhythmias are the immediate cause of several patient deaths [4]. Heparin oligosaccharides have a marked antiarrhythmic effect in an animal model of heart ischemia-reperfusion, as well as in isolated rat atria, reducing both ventricular arrhythmias and atrioventricular block, likely by increasing Na + -Ca 2+ exchanger activity [6].…”

Direct oral anticoagulation and severe obesity – One size fits all?

“…Particularly inflammatory and metabolic remodeling of the epicardial fat depot and its inter-organ communication with the atrial myocardium and blood compartment is increasingly considered to govern obesity-driven AF and thrombosis [13] , [14] . DOAC interfere in this self-perpetuating cross-talk to suppressing obesity-driven inflammatory sequelae and reducing atrial fibrosis and electrical remodeling in various experimental models (reviewed in [15] ). Mechanistically, this can be attributed to reduced signalling through protease-activated receptors (PAR), a family of four G-protein coupled receptors activated by proteolytic cleavage of the extracellular domain in response to thrombin, FXa and other serine proteases.…”

Stroke prevention of atrial fibrillation: Improving geographic under-use of contemporary antithrombotic approaches remains a challenge

“…The concerns about VKAs prompted the development of newer non-VKA oral anticoagulants (NOACs) with improved efficacy and a better safety profile as evidenced by large randomized controlled trials and real-world investigations [6] , [7] , [8] , [9] . Additionally, NOACs might also exert antiarrhythmic effects [10] . Due to the easy handling of NOACs for both physicians and patients compared to VKAs, the introduction of NOACs a decade ago has progressively replaced the classical VKAs in the prevention of stroke in AF patients.…”