scholarly journals Atrial Fibrillation: A Review of Recent Studies with a Focus on Those from the Duke Clinical Research Institute

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Meena P. Rao ◽  
Sean D. Pokorney ◽  
Christopher B. Granger
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
The United States ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Number Of Patients ◽  
Worse Prognosis ◽  
Research Institute

Atrial fibrillation is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States. The prevalence of atrial fibrillation averages 1% and increases with age. With the aging of the population, the number of patients with atrial fibrillation is expected to increase 150% by 2050, with more than 50% of atrial fibrillation patients being over the age of 80. This increasing burden of atrial fibrillation will lead to a higher incidence of stroke, as patients with atrial fibrillation have a five- to sevenfold greater risk of stroke than the general population. Strokes secondary to atrial fibrillation have a worse prognosis than in patients without atrial fibrillation. Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in atrial fibrillation. This review will summarize the experience of anticoagulants in patients with atrial fibrillation with a focus on the experience at the Duke Clinic Research Institute.

Old and new anticoagulants

2011 ◽  
Vol 31 (01) ◽  
pp. 21-27 ◽  
Author(s):  
U. Harbrecht
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Clotting Factor ◽  
Direct Thrombin Inhibitors ◽  
Self Monitoring ◽  
New Anticoagulants ◽  
Gastrointestinal Side Effects

SummaryVitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety.This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other “xabanes” currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making “anticoagulation bridging” unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them.Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.

scholarly journals A REVIEW ON A COMPARATIVE STUDY ON EFFECTIVENESS AND SAFETY OF NOVEL ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Priyanka P K ◽  
Mathew George ◽  
Lincy Joseph
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Therapeutic Option ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Systemic Embolism ◽  
Anticoagulant Drugs

Atrial fibrillation (AF) is characterized as an extremely rapid and disorganized atrial activation. These irregular heartbeats will cause blood to collect within the heart and potentially form a clot, which can travel to a person’s brain and cause a stroke. AF increases stroke risk by 3 to 5 fold. Vitamin K antagonists (VKAs) are highly effective for the prevention of stroke, mainly of ischemic origin, in patients with AF. For this reason, VKAs are currently recommended in all AF patients at moderate to high risk for stroke or systemic embolism (SSE). VKAs have significant limitations, particularly their unpredictable anticoagulant response and numerous food and drug interactions, mandating regular laboratory monitoring. These limitations make treatment with VKAs problematic for many patients; as a result, only about half of all potentially eligible AF patients are treated with VKAs. Over the last several years, novel oral anticoagulant drugs (NOACs), including direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban & rivaroxaban), have been developed. New orally administered anticoagulant drugs have emerged as potential alternatives to VKAs for the prevention of ischaemic stroke or systemic embolism in patients with chronic atrial fibrillation. Novel oral anticoagulants (NOACs), due to their a lot of predictable therapeutic result and more favorable haemorrhagic risk profile, represent a particularly attractive therapeutic option in AF patients. Keywords:  Novel oral anticoagulants (NOACs), Vitamin K antagonist (VKAs), Atrial fibrillation, Apixaban, Dabigatran, Rivaroxaban.

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.

scholarly journals Stroke-prevenció időskorban: az edoxabán hatékonysága és biztonságossága idős betegekben az ENGAGE AF vizsgálat eredményei alapján

2018 ◽  
Vol 159 (20) ◽  
pp. 798-802
Author(s):  
László Márk
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
The Elderly ◽  
Thromboembolic Events ◽  
Systemic Embolization ◽  
Number Of Patients ◽  
Net Clinical Benefit

Abstract: Atrial fibrillation is the most common clinically relevant arrhythmia frequently causing systemic thromboembolic events. Traditionally vitamin K antagonists had been used for decades to prevent these events. The emerging of the new direct anticoagulants has revolutionized this treatment and a gradual growth and extensive spread of usage is expected. The latest one approved in Hungary, edoxaban, is a factor Xa inhibitor. Once-daily administration and favourable safety profile are major benefits of this drug. In a large clinical study with a high number of patients it proved to be at least as effective as warfarin in the prevention of stroke and systemic embolization while causing significantly less major bleedings. As the incidence of atrial fibrillation increases with age, the observation that, compared with the other direct oral anticoagulants, the administration of edoxaban in the elderly has a favourable net clinical benefit (in the rate of prevented thromboembolic events and the number of caused bleedings) may have a great importance. Orv Hetil. 2018; 159(20): 798–802.

The NOACs: clinical pharmacology

ESC CardioMed ◽  
2018 ◽  
pp. 268-272
Author(s):  
Jeffrey Weitz
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Active Site ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

New anticoagulants – towards the development of an "ideal" anticoagulant

VASA ◽  
2009 ◽  
Vol 38 (1) ◽  
pp. 13-29 ◽  
Author(s):  
Haas
Keyword(s):  
Unfractionated Heparin ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Factor Xa ◽  
Rapid Onset ◽  
Factor Ix ◽  
Thrombin Inhibitors ◽  
Therapeutic Monitoring ◽  
Direct Thrombin Inhibitors ◽  
Onset Of Action

Currently available anticoagulants, such as unfractionated heparin, low molecular weight heparins and vitamin K antagonists, have proved effective in the prevention and treatment of thromboembolic disorders. However, these drugs have some drawbacks, such as unpredictability (in the case of unfractionated heparin), non-specificity and parenteral mode of administration, which limit their use in the clinical setting. There is a need for new agents with efficacy similar to that of these classes of anticoagulants and none of their associated drawbacks. Advances are being made in the development of more convenient and more specific drugs, with the aim to improve substantially the prevention and management of thromboembolic disorders. This review will emphasize how the development of an ideal anticoagulant, with potential benefits including high efficacy, safety, low levels of bleeding, fixed dosing, rapid onset of action, ability to bind clot-bound coagulation factors and no requirement for therapeutic monitoring, is a considerable challenge. This review will present the most relevant preclinical data, as well as the clinical studies performed to date, for several drug classes. Direct thrombin inhibitors, such as dabigatran etexilate, will be reviewed, as well as indirect (fondaparinux and idraparinux) and direct (rivaroxaban, apixaban, among others) Factor Xa inhibitors, Factor IXa inhibitors and monoclonal antibodies against Factor IX/IXa.

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