scholarly journals A Recent Update on Oral Anticoagulants

2021 ◽  
pp. 834-840
Author(s):  
Jijnasha Mishra ◽  
Shreem Deolia ◽  
Sunil Kumar
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Onset Of Action ◽  
Abrupt Decrease ◽  
Parenteral Route ◽  
Frequent Monitoring ◽  
The Brain ◽  
Better Than

Atrial Fibrillation is very common among Americana; it is the irregular rhythm of the heart usually present with or without symptoms. It causes the formation of clots, clots go to the brain and cause a stroke. Anticoagulants have been known for a few decades to cause abrupt decrease around 50%) in the rate of stroke and prevent clotting at the required location and can cause bleeding. Anticoagulants aims for the safeguard and therapy of thromboembolism to prevent stroke. Previously used Anticoagulants are Warfarin, low molecular weight heparin and heparin. There were shortcoming of the drugs like parenteral route of administration, requires frequent monitoring due to variability in response, the onset of action is slow and there is bleeding in response to the drugs .In addition to heparin and vitamin k antagonist, anticoagulants that act on enzymatic agility or vigor brought about by of thrombin and factor Xa was exquisitely formulated. Implementation of the foresaid oral Anticoagulants requires knowledge of necessitate the comprehension of discrete indication, contraindications, characteristics. Research and repeated clinical trials have led to acceptance of few newer drugs which are working classically styled but better than Warfarin. In the last few years, Pradaxa (dabigatran), Xarelto (rivaroxaban), and Eliquis (dabigatran) have all been authorised by the FDA (apixaban). All three are ‘blood thinners,’ like warfarin, that lessen the overall risk of stroke associated with atrial fibrillation while also causing bleeding.

Non–Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation

2019 ◽  
Vol 70 (1) ◽  
pp. 61-75 ◽  
Author(s):  
Alexander C. Fanaroff ◽  
E. Magnus Ohman
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Significant Risk ◽  
Vitamin K Antagonist ◽  
Therapeutic Window ◽  
Mechanical Valves ◽  
Frequent Monitoring

Atrial fibrillation (AF) increases a patient's stroke risk four- to five-fold. Anticoagulation with the vitamin K antagonist (VKA) warfarin reduces the risk of stroke by 67%, but warfarin carries a significant risk of major bleeding and has unpredictable pharmacodynamics with a narrow therapeutic window, necessitating frequent monitoring of its anticoagulant effect. The non–vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban provide more predictable anticoagulant activity than warfarin with a lower risk of major bleeding, and each is noninferior to warfarin for the prevention of stroke. All have earned regulatory approval in the past eight years. At least one of the NOACs is approved for use in all patients with AF, except those with mechanical valves and rheumatic mitral valve disease, for whom warfarin remains the only option. Recent clinical trials have shown that antithrombotic regimens including NOACs are safe and effective in patients with AF who need potent antiplatelet therapy.

scholarly journals The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Prudhvi Battula ◽  
Jose Otero ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemoglobin Concentration ◽  
Thrombin Inhibitor ◽  
Free Hemoglobin ◽  
Intracranial Hemorrhages ◽  
The Brain

Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

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.

scholarly journals Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board

2020 ◽  
Vol 28 (10) ◽  
pp. 504-513 ◽  
Author(s):  
B. A. Mulder ◽  
J. ten Berg ◽  
H. ten Cate ◽  
N. van Es ◽  
M. E. W. Hemels ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Treatment Guidelines ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Daily Practice ◽  
Advisory Board ◽  
Vascular Surgeon ◽  
Clinical Scenarios

Abstract The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

scholarly journals Type 2 Diabetes, Atrial Fibrillation, and Direct Oral Anticoagulation

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Dana Prídavková ◽  
Matej Samoš ◽  
Tomáš Bolek ◽  
Ingrid Škorňová ◽  
Jana Žolková ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Clinical Course ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Current Data ◽  
Thrombin Inhibitor

Type 2 diabetes (T2D) is an independent risk factor of stroke and systemic embolism in patients with atrial fibrillation (AF), and T2D patients with AF-associated stroke seem to have worse clinical outcome and higher risk of unfavorable clinical course compared to individuals without this metabolic disorder. Long-term anticoagulation is indicated in majority of T2D patients with AF to prevent adverse AF-associated embolic events. Direct oral anticoagulants (DOACs), direct oral thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have emerged as a preferred choice for long-term prevention of stroke in AF patients offering potent and predictable anticoagulation and a favorable pharmacology with low risk of interactions. This article reviews the current data regarding the use of DOACs in individuals with T2D and AF.

Breakthrough Stroke During Rivaroxaban Therapy in a Patient with Non-Valvular Atrial Fibrillation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4370-4370
Author(s):  
Inhye E Ahn ◽  
Myungsun Kim
Keyword(s):  
Atrial Fibrillation ◽  
Intracranial Hemorrhage ◽  
Therapeutic Dose ◽  
Conflicts Of Interest ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Mechanical Thrombolysis ◽  
Cerebral Angiogram ◽  
First Case ◽  
Pharmacodynamic Profile

Abstract Abstract 4370 Introduction. Rivaroxaban is the first orally active direct factor Xa inhibitor FDA approved for anticoagulation in non-valvular atrial fibrillation. Rivaroxaban has several remarkable aspects-it has less incidence of fatal bleeding and intracranial hemorrhage compared to Warfarin, excellent pharmacodynamic profile as an oral agent (high bioavailability (80–100%) and short half-life (7 to 11 hours), and it is reversible- which highlights Rivaroxaban as a promising future anticoagulant. However, 1.71% of Rivaroxaban arm in ROCKET-AF (New Eng J Med 2011;365:883-91) trial developed breakthrough stroke or systemic embolism while on therapeutic dose. We present the first report of breakthrough stroke in a patient with non-valvular atrial fibrillation anticoagulated with Rivaroxaban. Case presentation. A 52-year-old Caucasian male with non-valvular atrial fibrillation presented with aphasia, right-sided weakness and right facial droop. The patient was newly started on Rivaroxaban for two weeks followed by successful elective cardioversion a day prior to admission. One hour prior to admission, the patient was found with global aphasia, right hemianopsia and hemiparesis consistent with left MCA stroke. Ischemic CVA was confirmed with non-contrast CT. The patient underwent emergent cerebral angiogram and successful mechanical thrombolysis (Solitaire) of left MCA embolus. A week later, neurologic condition improved to hemiparetic and independent gait with residual dysarthria and right facial droop. Given his breakthrough embolic event, the choice of anticoaulgation was changed to Dabigatran. Conclusion. We have demonstrated the first case of breakthrough stroke while on therapeutic dose of Rivaroxaban in a patient with non-valvular atrial fibrillation. In a subset of patients with ischemic stroke while on therapeutic doses of oral anticoagulants, mechanical thrombolysis is crucial and intravenous thrombolytics should be avoided to minimize risk of intracranial hemorrhage. The effectiveness of alternative anticoagulation after failing Rivaroxaban needs to determined with further studies. Disclosures: No relevant conflicts of interest to declare.

Advances in Atrial Fibrillation-related Stroke Prevention

2015 ◽  
Vol 9 (2) ◽  
pp. 122
Author(s):  
Pierre Amarenco ◽  
Werner Hacke ◽  
Bo Norrving ◽  
Natalia Rost ◽  
◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Anticoagulant Therapy ◽  
Stroke Prevention ◽  
Stroke Risk ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Haemorrhagic Stroke ◽  
Bleeding Events ◽  
Patients At Risk

In patients with atrial fibrillation (AF) the risk of stroke is substantially increased, especially in those who are elderly (over 75 years) or have risk factors such as previous stroke, heart failure or hypertension. Stroke outcomes are also generally much worse in those with AF. Current guidelines indicate that any patient with AF and risk factors for stroke should receive anticoagulant therapy to limit their stroke risk. Despite these established recommendations, only 50 % of patients at risk receive anticoagulation with a vitamin K antagonist (VKA) and only 50 % of those are within the therapeutic range, indicating lack of adherence to the guidelines. Withholding anticoagulant therapy is mainly left to an individual physician’s choice, as shown in the ongoing GARFIELD registry of AF stroke prevention practice. Many physicians fear the risk of intracranial haemorrhage (ICH) for which outcomes remain poor. Recent clinical studies have shown that the non-VKA oral anticoagulants (NOACs) (apixaban, rivaroxaban, dabigatran and edoxaban) significantly reduce the risk of ICH and other bleeding events, while having non-inferior stroke prevention to warfarin. Use of these drugs, limiting exposure to aspirin and alcohol and controlling blood pressure have been shown to minimise ICH risk in large clinical trials and meta-analyses. Recent data from the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation (ENGAGE AF)-TIMI 48 study showed that the factor Xa inhibitor edoxaban was non-inferior to well-managed warfarin for reducing all stroke risk, and significantly reduced haemorrhagic stroke, major bleeding, ICH and death. These findings further support the case for using NOAC therapy for stroke prevention in patients with AF and risk factors for stroke.

scholarly journals The role of edoxaban in preventing thromboembolic complications in patients with atrial fibrillation

2020 ◽  
pp. 28-43
Author(s):  
O. O. Shakhmatova
Keyword(s):  
Atrial Fibrillation ◽  
Drug Interactions ◽  
Dose Reduction ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Extensive Study ◽  
Thromboembolic Complications ◽  
Nonvalvular Atrial Fibrillation ◽  
Life Threatening

Edoxaban is a selective direct factor Xa inhibitor. Edoxaban in a dose of 60 mg per day is an effective and safe option in the prevention of thromboembolic complications in patients with nonvalvular atrial fibrillation, including in combination therapy in patients after percutaneous coronary interventions. ENGAGE AF-TIMI 48 is currently the most extensive study comparing direct oral anticoagulants and warfarin in patients with atrial fibrillation, both in terms of number of participants and duration of observation. For edoxaban, an adequate approach to dose reduction has been developed in patients with alikely increase in plasma concentration due to renal impairment, low body weight or inter-drug interactions. Such dose reduction does notlead to an increase in the frequency of ischemic complications.Edoxaban is characterized by an optimal safety profile in patients with chronic moderate kidney disease, a small number of drug interactions and a convenient mode of administration. In patients with atrial fibrillation and concomitant ischemic heart disease, the use of Edoxaban is associated with a decrease in the frequency of myocardial infarctions, as well as strokes and episodes of systemic thromboembolism in comparison with warfarin. The drug can be successfully used as anticoagulant support for cardioversion and catheter ablation for atrial fibrillation.Edoxaban intake does not require routinelaboratory control. In case of unexpected situations (life-threatening bleeding, urgent surgical intervention) in patients receiving edoxaban, to assess the degree of anticoagulation should use the determination of anti-Xa activity. Clinical studies of a specific antidote of edoxaban - andexanet alfa are ongoing. Before approval of the specific antidote in severe andlife-threatening bleedings against the background of edoxaban administration, the use of prothrombin complex concentrate should be considered. Data on the effective and safe use of edoxaban in routine clinical practice have been accumulated.

The NOACs in special situations: the elderly, renal impairment, combination with antiplatelet agents and thrombolytics

ESC CardioMed ◽  
2018 ◽  
pp. 273-278
Author(s):  
Felicita Andreotti ◽  
Eliano Pio Navarese ◽  
Filippo Crea
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Antiplatelet Agents ◽  
Clinical History ◽  
The Elderly ◽  
Arterial Disease ◽  
Baseline Risk

Phase III randomised trials indicate that the non-vitamin K antagonist oral anticoagulants (NOACs) are preferable to warfarin in elderly, non-valvular atrial fibrillation patients, given a lower incidence of intracranial haemorrhage, a favourable overall efficacy and safety profile, and the lack of routine monitoring, although care is needed to dose-adjust for kidney function and to prevent gastrointestinal bleeds, depending on the NOAC. Advanced age should not exclude the use of any NOAC. Overall, NOACs perform well, relative to warfarin or aspirin, irrespective of renal function. However, all NOACs undergo variable renal clearance, and in Europe a creatinine clearance of less than 30 mL/min contraindicates dabigatran and less than 15 mL/min the factor Xa inhibitors. Trial outcomes stratified by antiplatelet therapy, after adjustment for baseline risk, show that concomitant antiplatelet use does not significantly alter the overall treatment effects of NOACs versus warfarin. Whether adding an antiplatelet to a NOAC in atrial fibrillation patients with arterial disease is beneficial requires randomized controlled testing. Current guidelines recommend that patients effectively anticoagulated with a NOAC who develop an acute ischaemic stroke should not be considered for thrombolysis unless clinical history or laboratory tests indicate low or no anticoagulation or at least two half-lives have elapsed from the last NOAC dose. Retrospective data suggest no prohibitive adverse events among selected NOAC-treated patients with acute ischaemic stroke receiving thrombolysis. Further investigation in this setting is warranted.

How I treat target-specific oral anticoagulant–associated bleeding

Blood ◽  
2014 ◽  
Vol 123 (8) ◽  
pp. 1152-1158 ◽  
Author(s):  
Deborah M. Siegal ◽  
David A. Garcia ◽  
Mark A. Crowther
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Clinical Evidence ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Supportive Therapy ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Life Threatening

Abstract Target-specific oral anticoagulants (TSOACs) that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are effective and safe alternatives to vitamin K antagonists (VKAs) and low-molecular-weight heparin (LMWH). Although these agents have practical advantages compared with VKAs and LMWH, there are no antidotes that reverse their anticoagulant effect. Clinical evidence for the efficacy of nonspecific therapies that promote formation of fibrin (prothrombin complex concentrate [PCC], activated PCC [aPCC], and recombinant factor VIIa) in the setting of TSOAC-associated bleeding is lacking, and these prohemostatic products are associated with a risk of thrombosis. In the absence of specific antidotes, addition of PCC or aPCC to maximum supportive therapy may be reasonable for patients with severe or life-threatening TSOAC-associated bleeding. Targeted antidotes for these agents are in development.

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