Electrophysiological effects of non-vitamin K antagonist oral anticoagulants on atrial repolarizing potassium channels.

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology
Felix WiedmannDierk Thomas

Abstract

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. This study was designed to elucidate acute pharmacological effects of NOACs on cloned ion channels Kv11.1, Kv1.5, Kv4.3, Kir2.1, Kir2.2, and K2P2.1 contributing to IKr, IKur, Ito, IK1, and IK2P 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 Kv11.1, Kv1.5, Kv4.3, Kir2.1, Kir2.2, or K2P2.1 K+ channels. Furthermore, biophysical characterization did not reveal significant effects ...Continue Reading

References

Sep 1, 2009·The New England Journal of Medicine·Stuart J ConnollyUNKNOWN RE-LY Steering Committee and Investigators
Apr 6, 2011·Circulation·Graeme J Hankey, John W Eikelboom
Apr 15, 2011·Vascular Health and Risk Management·Constanze SchmidtDierk Thomas
Aug 13, 2011·The New England Journal of Medicine·Manesh R PatelUNKNOWN ROCKET AF Investigators
Aug 30, 2011·The New England Journal of Medicine·Christopher B GrangerUNKNOWN ARISTOTLE Committees and Investigators
Mar 19, 2013·Journal of Biomedical Science·Chien-Jung ChangYi-Jen Chen
Nov 21, 2013·The New England Journal of Medicine·Robert P GiuglianoUNKNOWN ENGAGE AF-TIMI 48 Investigators
Nov 6, 2014·The New England Journal of Medicine·Jack E AnsellJames C Costin
Nov 4, 2016·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Paulus KirchhofKatja Zeppenfeld
Mar 3, 2018·Circulation Research·Jordi HeijmanStanley Nattel
Jul 19, 2018·European Journal of Pharmacology·Chien-Jung ChangYi-Jen Chen
May 6, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Anke C FenderDobromir Dobrev

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Electrophysiology

Cardiac electrophysiology is the study of electrical activities of the heart and includes the assessment, diagnosis, and treatment of cardiac events. Find the latest research on cardiac electrophysiology here.

Atrial Filbrillation

Atrial fibrillation refers to the abnormal heart rhythm characterized by rapid and irregular beating of the atria. Here is the latest research.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.