Warfarin versus dabigatran etexilate: an assessment of efficacy and safety in patients with atrial fibrillation

dabigatran etexilate, warfarin, oral anticoagulation, atrial fibrillation, efficacy, safety.Introduction Oral anticoagulation is the mainstay for stroke and thromboembolic events prevention in patients with atrial fibrillation (AF). Given limitations of warfarin therapy non-vitamin K oral anticoagulants have been developed, including direct thrombin inhibitors (i.e. dabigatran etexilate). Dabigatran etexilate has been tested thoroughly in terms of efficacy and safety in clinical trials and studies, involving 'real world' cohorts. In this review currently available evidence in patients with non-valvular AF is discussed. Areas covered The pharmacology, efficacy and safety, and current aspects of use of dabigatran etexilate in patients with non-valvular AF are reviewed in comparative manner to warfarin both for chronic anticoagulation and in different clinical settings. Expert opinion Dabigatran etexilate appeared to have several pharmacokinetic and pharmacodynamic advantages over warfarin as well as a favourable efficacy and safety profile being at least non-inferior and often superior to warfarin in patients with non-valvular AF. The latter was shown in the clinical trials, meta-analyses and studies with 'real world' data. Currently ongoing trials will expand the body of evidence on warfarin and will aid decision-making in currently controversial areas. Important limitations of dabigatran etexilate include contraindications for its use in patients with prosthetic heart valves and end-stage chronic kidney disease

Antithrombotic and anticoagulant therapy for atrial fibrillation

atrial fibrillation, stroke risk, bleeding risk, antithrombotic prophylaxis, oral anticoagulants, antiplatelet drugsAtrial fibrillation (AF) substantially increases the risk of stroke and other thromboembolic events. Hence, the vast majority of AF patients require appropriate antithrombotic prophylaxis. Oral anticoagulation (OAC) with either dose-adjusted vitamin K antagonist (VKA, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, e.g. dabigatran, apixaban, rivaroxaban) can be used for this purpose unless contraindicated. Therefore, stroke and bleeding risk assessment is an obligatory part of AF management and risk has to be weighed individually. Antiplatelet drugs (e.g. aspirin and clopidogrel) are inferior to OACs, both alone and in combination, with comparable risk of bleeding events. Exclusion of the left atrial appendage as major source of embolism in AF is an alternative option for stroke prevention in the few high risk patients with contraindications for anticoagulation

Antithrombotic and anticoagulant therapy for atrial fibrillation

atrial fibrillation, stroke risk, bleeding risk, antithrombotic prophylaxis, oral anticoagulants, antiplatelet drugsAtrial fibrillation (AF) substantially increases the risk of stroke and other thromboembolic events. Hence, the vast majority of AF patients require appropriate antithrombotic prophylaxis. Oral anticoagulation (OAC) with either dose-adjusted vitamin K antagonist (VKA, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, e.g. dabigatran, apixaban, rivaroxaban) can be used for this purpose unless contraindicated. Therefore, stroke and bleeding risk assessment is an obligatory part of AF management and risk has to be weighed individually. Antiplatelet drugs (e.g. aspirin and clopidogrel) are inferior to OACs, both alone and in combination, with comparable risk of bleeding events. Exclusion of the left atrial appendage as major source of embolism in AF is an alternative option for stroke prevention in the few high risk patients with contraindications for anticoagulation

Edoxaban for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation

edoxaban, warfarin, oral anticoagulation, atrial fibrillation, efficacy, safety.Introduction Oral anticoagulation is central to the management of patients with atrial fibrillation (AF) and at least one additional stroke risk factor. For decades, the vitamin K antagonists (e.g. warfarin) remained the only oral anticoagulant available for stroke prevention in AF. The non-vitamin K oral anticoagulants (NOACs) are now available, and these drugs include the direct thrombin inhibitors and factor Xa inhibitors. The latter class includes edoxaban that has recently been approved for stroke prevention in AF by United States Food and Drug Administration and European Medicine Agency. In line with other NOACs, edoxaban avoids the many limitations of warfarin associated with variability of anticoagulation effect and multiple food and drug interactions. Areas covered In this review, the currently available evidence on edoxaban in patients with non-valvular AF is discussed. The pharmacology, efficacy and safety, and current aspects of use of edoxaban in patients with non-valvular AF for stroke and thromboembolism prevention are reviewed. Expert opinion Phase III trial on edoxaban for stroke prevention in non-valvular AF confirms non-inferiority of edoxaban compared to well-managed warfarin both in terms of efficacy and safety. Currently ongoing and future trials as well as real-world data are warranted to confirm its effectiveness and safety for chronic anticoagulation and improve evidence in other areas which are lacking evidenc

Stroke and bleeding risk assessment: Where are we now?

AtrialFibrillation, Stroke, Bleeding, Risk Assessment.Atrial fibrillation (AF) is one of major problems of the contemporary cardiology. Ischaemic stroke is a common complication of the AF, and effective prophylaxis requires treatment with oral anticoagulants. The purpose of this current review article is to provide an overview of the various stroke and bleeding risk assessment scores that help decision making with respect to thromboprophylaxis. Particular focus is made on the currently guideline-recommended stroke and bleeding risk scores, such as CHA2DS2-VASc (congestive heart failure or left ventricular dysfunction, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74 and sex category [female]) and HAS-BLED (uncontrolled hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly [e.g. age >65, frail condition], drugs [e.g. aspirin, nonsteroidal anti-inflammatory drugs]/excessive alcohol) is made. Future directions for improvement of predictive ability of risk assessment with clinical factors and biomarkers are also discussed

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

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

antithrombotic prophylaxis, atrial fibrillation, coronary artery disease, percutaneous coronary interventioAtrial fibrillation (AF) and coronary artery disease (CAD) often coexist. Both conditions confer an increased risk of acute thrombotic complications. However, the pathogenesis of thrombus development in AF and CAD is different. Coagulation activation is the main pathway in AF, and platelet activation is the hallmark of coronary thrombosis. Antithrombotic prophylaxis is essential in both conditions. In patients with AF undergoing percutaneous coronary intervention (PCI), a combination of oral antico¬agulation and antiplatelet therapy is required, which elevates the risk of major bleeding. This has to be balanced against the risk of stroke and stent thrombosis. In the first part of the present review, the prerequisites for antithrombotic management in AF patients undergoing PCI are discussed. We cover the epidemiology of concomitant presentation of AF and CAD as well as differences in the pathogenesis of thrombus formation in both conditions. We evaluate data regarding a variety of antithrombotic regimens including triple therapy in line with stroke and bleeding risk assessment. Overall, triple therapy is often warranted but should be for the shortest possible duration. Although much of the current guidance comes from observational data, well designed, adequately powered randomized clinical trials are emerging to further inform practice in this challenging area

Stroke and bleeding risk in atrial fibrillation: navigating the alphabet soup of risk-score acronyms (CHADS2, CHA2DS2-VASc, R2CHADS2, HAS-BLED, ATRIA, and more)

: atrial fibrillation, stroke, bleeding, risk assessment.Stroke prevention is central to the management of patients with atrial fibrillation (AF). As effective stroke prophylaxis essentially requires oral anticoagulants (OAC) an understanding of the risks and benefits of OAC therapy is needed. While AF increases stroke risk 5-fold, this risk is not homogeneous. Many stroke risk factors also confer an increased risk of bleeding. Various stroke and bleeding risk stratification schemes have been developed to help inform clinical decision making. These scores were derived and validated in different study cohorts, ranging from highly selected clinical trial cohorts to 'real world' populations. Thus, their performance and classification accuracy varies depending on their derivation cohort(s). In the present review, we provide an overview of currently available stroke and bleeding risk stratification schemes. We particularly focus on the CHA2DS2-VASc and HAS-BLED schemes, as these are recommended by the latest European guidelines on AF management. Other risk stratification schemes (CHADS2, R2CHADS2, ATRIA, HEMORRHAGES, QStroke, etc.) and their place in the decision-making are also considered

Cardiac fibrosis in patients with atrial fibrillation: Mechanisms and clinical implications

atrial fibrillation, heart failure, cardiac fibrosisAtrial fibrillation (AF) is associated with structural, electrical and contractile remodeling of the atria. Development and progression of atrial fibrosis is the hallmark of structural remodeling in AF and is considered to be substrate for AF perpetuation. In contrast, experimental and clinical data on impact of ventricular fibrotic processes in pathogenesis of AF and its complications are controversial. Ventricular fibrosis appears to contribute to abnormalities in cardiac relaxation and contractility, and development of heart failure, a common finding in AF. Given the frequent coexistence of AF and heart failure and the fact that both conditions affect patient prognosis better understanding of mutual impact of fibrosis in AF and heart failure is of particular interest. In this review article, we provide an overview on the general mechanisms of cardiac fibrosis in AF, differences between fibrotic processes in atria and ventricles, and the clinical and prognostic significance of cardiac fibrosis in AF