scholarly journals Stroke Prevention in Atrial Fibrillation: Understanding the New Oral Anticoagulants Dabigatran, Rivaroxaban, and Apixaban

Thrombosis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Tan Ru San ◽  
Mark Yan Yee Chan ◽  
Teo Wee Siong ◽  
Tang Kok Foo ◽  
Ng Kheng Siang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Primary Care Physicians ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Fixed Dose ◽  
Thrombin Inhibitor ◽  
Factor X

Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)—direct thrombin inhibitor, dabigatran, and direct activated factor X inhibitors, rivaroxaban, and apixaban—do not require routine INR monitoring. Compared to VKAs, they possess relatively rapid onset of action and short halflives, but vary in relative degrees of renal excretion as well as interaction with p-glycoprotein membrane transporters and liver cytochrome P450 metabolic enzymes. Recent completed phase III trials comparing NOACs with VKAs for stroke prevention in atrial fibrillation (AF)—the RE-LY, ROCKET AF, and ARISTOTLE trials—demonstrated at least noninferior efficacy, largely driven by significant reductions in haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were acceptable compared to VKAs. Of note, the NOACs caused significantly less intracranial haemorrhagic events compared to VKAs, the mechanisms of which are not completely clear. With convenient fixed-dose administration, the NOACs facilitate anticoagulant management in AF in the community, which has hitherto been grossly underutilised. Guidelines should evolve towards simplicity in anticipation of greater use of NOACs among primary care physicians. At the same time, the need for caution with their use in patients with severely impaired renal function should be emphasised.

scholarly journals Ten years of non-vitamin K antagonists oral anticoagulants for stroke prevention in atrial fibrillation: is warfarin obsolete?

2020 ◽  
Vol 22 (Supplement_O) ◽  
pp. O28-O41
Author(s):  
Matthias Hammwöhner ◽  
Andreas Goette
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Data ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Study Data ◽  
Phase Iii ◽  
Clinical Settings ◽  
Specific Patient

Abstract Currently, four non-vitamin K antagonists oral anticoagulants (NOACs) are available for stroke prevention in atrial fibrillation (AF). These have been in clinical use for up to 10 years now. Besides data of the initial phase III clinical trials, now clinical data, several sub-studies, meta-analyses, and studies in special clinical settings and specific patient populations are available. This review shall give an overview on the history of NOAC development, sum up study data and ‘real-world’ clinical data as well as discuss several special clinical settings like NOAC treatment in patients that require coronary artery stenting or cardioversion (CV). Furthermore, treatment considerations in special patient populations like patients with renal impairment, obesity, or patients requiring NOACs for secondary prevention are discussed. The significance of NOAC treatment will be discussed under consideration of the recently published 2020 ESC/EACTS Guidelines for the diagnosis and management of AF.

scholarly journals Direct Oral Anticoagulants in Patients with Obesity and Atrial Fibrillation: Position Paper of Italian National Association of Hospital Cardiologists (ANMCO)

2021 ◽  
Vol 10 (18) ◽  
pp. 4185
Author(s):  
David Mocini ◽  
Stefania Angela Di Fusco ◽  
Edoardo Mocini ◽  
Lorenzo Maria Donini ◽  
Carlo Lavalle ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
High Body Mass Index ◽  
Normal Weight ◽  
Phase Iii ◽  
Fixed Dose ◽  
Pivotal Phase ◽  
Phase Iii Trials

The use of the direct oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban (DOACs) offers some major advantages over warfarin and other vitamin K antagonists (VKAs). One advantage is the possibility to use a fixed dose in normal-weight patients, overweight patients and patients with obesity. However, the “one size fits all” strategy raised a concern regarding the possibility to undertreat patients with a high body mass index. No randomized controlled trials (RCTs) have ever compared VKAs and DOACs in this population. We analyzed data from the literature on DOAC pharmacokinetics and pharmacodynamics, results from the four pivotal phase III trials on non-valvular atrial fibrillation, retrospective observational studies and metanalyses. While we are aware of the limitation imposed by the absence of specific RCTs, we propose the position of the Italian Association of Hospital Cardiologists (ANMCO) on the use of DOACs in patients with obesity based on the existing evidence.

scholarly journals Old and new oral anticoagulants for secondary stroke prevention in atrial fibrillation

2015 ◽  
Vol 9 (4) ◽  
pp. 314
Author(s):  
Tommaso Sacquegna ◽  
Anna Zaniboni ◽  
Andrea Rubboli ◽  
Gaetano Procaccianti ◽  
Michela Crisci ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Secondary Prevention ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Significant Difference

Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF), with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (<em>i.e</em>., dabigatran) and direct factor Xa inhibitors (<em>i.e</em>., apixaban and rivaroxaban) have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke) subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

Warfarin Versus New Agents: Interpreting the Data

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 221-228 ◽  
Author(s):  
Jack Ansell
Keyword(s):  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Thrombin Inhibitor ◽  
New Agents ◽  
New Class ◽  
Phase Iii Trials ◽  
Pros And Cons

AbstractStroke prevention in atrial fibrillation (AF) is a rapidly expanding indication for lifelong oral anticoagulation. The vitamin K antagonists (VKAs) effectively prevent stroke, but are notoriously difficult to manage and are associated with frequent adverse events. These factors account for the widespread underuse of warfarin for patients with AF who are qualified candidates for therapy. New oral anticoagulants with different mechanisms of action are beginning to exit phase III trials and may replace the VKAs for a number of indications, especially AF. The oral direct thrombin and Xa inhibitors are furthest along in development. Dabigatran etexilate, a thrombin inhibitor, has recently shown excellent outcomes in the prevention of stroke in patients with AF. The oral Xa inhibitors are still in phase III trials for stroke prevention in AF, but results from trials for other indications look promising. These short-acting, short-duration, unmonitored drugs are not without limitations and potential adverse effects. The perceived drawbacks of the VKAs may actually be assets in the management of patients with AF, and the pros and cons of each class of drug must be taken into account as physicians consider or patients request transition to a new class of oral anticoagulants.

Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation: Update and Periprocedural Management

2019 ◽  
Vol 39 (2) ◽  
pp. 54-67 ◽  
Author(s):  
Joya D. Pickett
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Fixed Dose ◽  
Thrombin Inhibitor ◽  
National Guidelines ◽  
Nonvalvular Atrial Fibrillation ◽  
Periprocedural Management

Vitamin K antagonists (eg, warfarin) have been the standard of care for stroke prophylaxis in atrial fibrillation. The direct oral anticoagulants dabigatran (direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (direct factor Xa inhibitors) are as efficacious as and in some instances superior to vitamin K antagonists in the prevention of stroke, systemic embolism, and major bleeding compared with warfarin for nonvalvular atrial fibrillation. Benefits of direct oral anticoagulants include a rapid onset of therapeutic effect, fixed dose-response relationships without the need for routine monitoring, a short half-life, and infrequent need for periprocedural bridging with a parenteral agent. However, direct oral anticoagulants differ in subsets of patients. Critical care and advanced practice nurses must understand these differences, prescribing considerations, drug aherence interventions, drug-drug interactions, and periprocedural management. This article presents an update and review of direct oral antigcoagulants based on the latest national guidelines.

Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation.

2011 ◽  
Vol 106 (11) ◽  
pp. 868-876 ◽  
Author(s):  
Luciano Crippa ◽  
Anna Falanga ◽  
Guido Finazzi ◽  
Francesco Marongiu ◽  
Gualtiero Palareti ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
New Drugs ◽  
New Oral Anticoagulants ◽  
Laboratory Control ◽  
Questions And Answers

SummaryDabigatran and other new oral anticoagulants (OAC) represent a step forward in stroke prevention in patients with atrial fibrillation (AF). They indeed have been shown to be an alternative to vitamin K antagonists (VKAs) without the burden of laboratory control. However, these new drugs compete with an effective and well-established therapy, thus bringing about a series of questions and doubts. In this report members of the board of the Italian Federation of Thrombosis Centers (FCSA) answer some questions every clinician might be confronted with.

scholarly journals Stroke Prevention in Atrial Fibrillation – Outcomes and Future Directions

2014 ◽  
Vol 3 (3) ◽  
pp. 194 ◽  
Author(s):  
Katrina Mountfort ◽  
John Camm ◽  
Gregory Lip ◽  
Andreas Goette ◽  
Jean-Yves Le Heuzey ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Major Bleeding ◽  
Stroke Prevention ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Phase Iii ◽  
Thrombin Inhibitor ◽  
Once Daily

Stroke prevention is central to the management of patients with atrial fibrillation (AF). Vitamin K antagonists (VKAs) are the established and long-standing option for stroke prevention therapy in patients with AF. However, non-VKA oral anticoagulants (NOACs) have recently been developed and demonstrated non-inferior efficacy vs VKA treatment, with fewer limitations in clinical practice and with reduced risks of major bleeding. In order to discuss the usage, efficacy and safety of NOACs, a satellite symposium was held at the Cardiostim/EHRA Europace Congress in Nice in June 2014. At present, three NOACs, a direct thrombin inhibitor (dabigatran) and two direct factor Xa inhibitors (rivaroxaban and apixaban) have been approved in Europe for stroke prevention in patients with AF. In addition, the once-daily factor Xa inhibitor edoxaban has recently been evaluated in this setting in the phase III Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation – Thrombolysis In Myocardial Infarction Study 48 (ENGAGE AF-TIMI 48) that compared edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin (international normalised ratio 2.0–3.0). ENGAGE AF-TIMI 48 was the largest trial with a NOAC to date, and demonstrated that both dosing regimens of once-daily edoxaban were non-inferior to well-managed warfarin treatment for the prevention of stroke or systemic embolism and also provided significant reductions in the risk of haemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. In summary, the recent availability of NOACs has enabled physicians to avoid the limitations of VKA therapy in clinical practice and tailor anticoagulant treatment to the individual patient. However, worldwide usage of oral anticoagulant therapy remains suboptimal compared with guideline recommendations, and further dissemination of its benefits may prove helpful.

scholarly journals Optimal Anticoagulation Strategy for Cardioversion in Atrial Fibrillation

2015 ◽  
Vol 4 (1) ◽  
pp. 44 ◽  
Author(s):  
Philipp Bushoven ◽  
Sven Linzbach ◽  
Mate Vamos ◽  
Stefan H Hohnloser ◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Prospective Trial ◽  
Bleeding Complications ◽  
Order Of Magnitude ◽  
Pharmacological Cardioversion

For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.

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