Non-vitamin K oral anticoagulants in atrial fibrillation:Where are we now?

atrial fibrillation, non-vitamin K oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, warfarinAtrial fibrillation (AF) confers increased risk of stroke and other thromboembolic events, and oral anticoagulation therefore is the essential part of AF management to reduce the risk of this complication. Until recently, the vitamin K antagonists (VKAs, e.g. warfarin) were the only oral anticoagulants available, acting by decreased synthesis of vitamin K-dependent coagulation factors (II, VI, IX, and X). The VKAs had many limitations: delayed onset and prolonged offset of action, variability of anticoagulant effect among patients, multiple food and drug interactions affecting pharmacological properties of warfarin, narrow therapeutic window, obligatory regular laboratory control, which all made warfarin 'inconvenient' both for patients and clinicians. The limitations of VKAs led to development of new class of drugs collectively defined as non-VKA oral anticoagulants (NOACs), which included direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban). The NOACs avoid many of the VKA drawbacks. In this review we will focus on the current evidence justifying use of NOACs in non-valvular AF

Effects of Aspirin on Endothelial Function and Hypertension

PURPOSE OF REVIEW: Endothelial dysfunction is intimately related to the development of various cardiovascular diseases, including hypertension, and is often used as a target for pharmacological treatment. The scope of this review is to assess effects of aspirin on endothelial function and their clinical implication in arterial hypertension. RECENT FINDINGS: Emerging data indicate the role of platelets in the development of vascular inflammation due to the release of proinflammatory mediators, for example, triggered largely by thromboxane. Vascular inflammation further promotes oxidative stress, diminished synthesis of vasodilators, proaggregatory and procoagulant state. These changes translate into vasoconstriction, impaired circulation and thrombotic complications. Aspirin inhibits thromboxane synthesis, abolishes platelets activation and acetylates enzymes switching them to the synthesis of anti-inflammatory substances. SUMMARY: Aspirin pleiotropic effects have not been fully elucidated yet. In secondary prevention studies, the decrease in cardiovascular events with aspirin outweighs bleeding risks, but this is not the case in primary prevention settings. Ongoing trials will provide more evidence on whether to expand the use of aspirin or stay within current recommendations

Direct oral anticoagulant reversal: how, when and issues faced

Introduction: The number of atrial fibrillation (AF) patients requiring thrombo-prophylaxis with oral anticoagulation is greatly increasing. The introduction of non-vitamin K oral anticoagulants (NOACs) in addition to standard therapy with dose-adjusted warfarin has increased the therapeutic options for AF patients. Despite a generally better safety profile of the NOACs, the risk of major bleedings still persists, and the management of serious bleeding is a clinical challenge. Areas covered: In the current review, risk of major bleeding in patients taking NOACs and general approaches to manage bleeding depending on severity, with a particular focus on specific reversal agents, are discussed. Expert commentary: Due to short half-life of NOACs compared to warfarin, discontinuation of drug, mechanical compression, and volume substitution are considered to be sufficient measures in most of bleeding cases. In case of life-threatening bleeding or urgent surgery, hemostasis can be achieved with non-specific reversal agents (prothrombin complex concentrates) in patients treated with factor Xa inhibitor until specific antidotes (andexanet α and ciraparantag) will receive approval. Thus far, idarucizumab has been the only reversal agent approved for dabigatran

Patients with atrial fibrillation undergoing percutaneous coronary intervention. Current concepts and concerns:part I

antithrombotic prophylaxis, atrial fibrillation, coronary artery disease, percutaneous coronary interventionAtrial fibrillation (AF) and coronary artery disease (CAD) often present concomitantly. Given the increased risk of thrombotic complications with either of them but different pathogenesis of clot formation, combined antithrombotic therapy is necessary in patients developing acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI). Different antithrombotic regimens in this group of patients have been summarized and discussed earlier. Triple therapy remains the treatment of choice in these patients despite the increased risk of hemorrhagic complications. Given the absence of evidence from randomized controlled trials, balancing the risk of stroke and stent thrombosis against the risk of major bleeding is a challenge. Precise stroke and bleeding risk assessment is an essential part of the decision making process regarding antithrombotic management. Continuing the discussion of current concepts and concerns of antithrombotic management in AF patients undergoing PCI, we emphasize the importance of various strategies to reduce bleeding in the modern era, namely, radial access combined with careful selection of a P2Y₁₂ receptor inhibitor, use of newer drug-eluting stents, and uninterrupted anticoagulation for patients undergoing procedures. We also focus on the role of the non-vitamin K oral anticoagulants (novel oral anticoagulants, eg, dabigatran, rivaroxaban, apixaban, and edoxaban) which are increasingly used for stroke prevention in AF. Finally, recent recommendations on the management of antithrombotic therapy in AF patients presenting with acute coronary syndrome and/or undergoing PCI as well as ongoing clinical trials and future directions are highlighted