Electrophysiological effects of non-vitamin K antagonist oral anticoagulants on atrial repolarizing potassium channels. Issue 9 (17th July 2020)

• Record Type: Journal Article
• Authors: Wiedmann, Felix; Schlund, Daniel; Kraft, Manuel; Nietfeld, Jendrik; Katus, Hugo A; Schmidt, Constanze; Thomas, Dierk
• Is Part Of: Europace. Volume 22:Issue 9(2020)
• Page Start: 1409
• Page End: 1418
• Publication Date: 2020-07-17
• Subjects: Anticoagulation -- Atrial fibrillation -- Ion channel -- Non-vitamin K antagonist oral anticoagulant; Arrhythmia -- Treatment -- Periodicals; Cardiac pacing -- Periodicals; Catheter ablation -- Periodicals; Heart -- Physiology -- Periodicals; Electrophysiology -- Periodicals; 617.4120645
• DOI: 10.1093/europace/euaa129
• Languages: English
• ISSNs: 1099-5129

Abstract

Abstract: Aims : Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). The efficacy of NOACs has been attributed in part to pleiotropic effects that are mediated through effects on thrombin, factor Xa, and their respective receptors. Direct pharmacological effects of NOACs and cardiac ion channels have not been addressed to date. We hypothesized that the favourable clinical outcome of NOAC use may be associated with previously unrecognized effects on atrial repolarizing potassium channels. Methods and results : This study was designed to elucidate acute pharmacological effects of NOACs on cloned ion channels Kv 11.1, Kv 1.5, Kv 4.3, Kir 2.1, Kir 2.2, and K2P 2.1 contributing to I Kr, I Kur, I to, I K1, and I K2P K + currents. Human genes, KCNH2, KCNA5, KCND3, KCNJ2, KCNJ12, and KCNK2, were heterologously expressed in Xenopus laevis oocytes, and currents were recorded using voltage-clamp electrophysiology. Apixaban, dabigatran, edoxaban, and rivaroxaban applied at 1 µM did not significantly affect peak current amplitudes of Kv 11.1, Kv 1.5, Kv 4.3, Kir 2.1, Kir 2.2, or K2P 2.1 K + channels. Furthermore, biophysical characterization did not reveal significant effects of NOACs on current–voltage relationships of study channels. Conclusion : Apixaban, dabigatran, edoxaban, and rivaroxaban did not exhibit direct functional interactions with human atrial K + channels underlying I Kr, I Kur, I to, I K1, and I K2P currents that could account for beneficial clinical outcome associated with the drugs. Indirect or chronic effects and potential underlying signalling mechanisms remain to be investigated.