PAR1 contribution in acute electrophysiological properties of oral anticoagulants in rabbit pulmonary vein sleeve preparations.

Whether oral anticoagulants, vitamin K antagonists (VKAs), and nonvitamin K oral anticoagulant (NOACs) frequently prescribed to atrial fibrillation (AF) patients, do themselves have a pro- or anti-arrhythmic effect have never been addressed. Transmembrane action potentials were recorded in an acute rabbit model of superfused pulmonary veins (PVs) sleeves preparations using standard microelectrode technique. Fluindione 10 µm (n = 6) increased the AP (action potential) duration (APD), induced a significantly Vmax depression (from 95 ± 14 to 53 ± 5 V/s, P < 0.05), and 2 : 1 blocks during rapid atrial pacing thus evoking class I anti-arrhythmic properties, and prevented spontaneous trigger APs. Apixaban 10 µm (n = 6) increased the APD, significantly prolonged the effective refractory period (from 56.3 ± 4.2 to 72.0 ± 8.6 ms, P < 0.05), and prevented triggered APs occurrence. Fluindione and apixaban effects were suppressed with the addition of the protease-activated receptors 1 (PAR 1) agonist SFLLR-NH2 . Warfarin 10 µm (n = 6) significantly abbreviated the early refractory period (from 56.3 ± 4.2 to 45.0 ± 2.2 ms, P < 0.05) and increased triggered APs occurrence that were successfully prevented by nifedipine but not by the addition of the protease-activated receptors 1 agonist SFLLR-NH2 . In this acute rabbit PVs model, VKAs and NOACs, at physiological concentrations, exhibited very different pharmacological properties that influence PVs electrophysiology, implying PAR1, with fluindione and apixaban which exhibited more anti-arrhythmic properties, whereas warfarin exhibited more pro-arrhythmic properties.

Non-vitamin K oral anticoagulant treatment in elderly patients with atrial fibrillation and coronary heart disease.

Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Overall prevalence is estimated to 5.5% and the incidence increases with age. As the population ages, the prevalence and costs of AF are expected to increase. AF is the most important cause of stroke in patients >75years. Until recently, Vitamin K antagonists (VKAs) were the only available oral anticoagulants (OACs) evaluated for long-term treatment of patients with AF with or without coronary heart disease (CHD). This situation was challenged by introduction of non-VKA oral anticoagulants (NOACs). In AF, use of NOACs seems to be as effective and safe as VKAs, especially in elderly patients. AF and CHD are frequently associated and the question of antithrombotic management in aging patients is delicate. In elderly patients experiencing a new AF episode after an acute coronary syndrome, triple antithrombotic therapy should be as short as possible in order to decrease the risk of major bleedings. To date, there is no specific study or available guidelines regarding the NOACs use specifically in elderly patients experiencing both AF and CHD. In this review, we try to provide a perspective on NOACs future incorporation into clinical practice in elderly patients with both AF and CHD.