Direct Oral Anticoagulants

2017 ◽  
Author(s):  
Panna A. Codner ◽  
Michael G Mount
Keyword(s):  
Perioperative Management ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Clinical Use ◽  
Nonvalvular Atrial Fibrillation ◽  
Reversal Agents

Non–vitamin K antagonist oral anticoagulants, also known as direct oral anticoagulants, are a relatively recent class of medications introduced into clinical practice. Due to their safety profiles, fixed dosing, and lack of need for frequent laboratory monitoring, they are becoming preferred to traditional anticoagulation with warfarin in many cases of nonvalvular atrial fibrillation and venous thromboembolism. Currently, four drugs are available: dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, factor Xa inhibitors. This review covers the pharmacology, monitoring, and reversal agents currently available for these medications. The indications for their use are covered through a review of the major clinical trials that led to their US and European approvals for clinical use. Perioperative management of these medications is discussed. Tables list indications, dosing, and monitoring, as well as bleeding risks and efficacy compared with warfarin.  This review contains 1 figure, 11 tables, and 70 references. Key words: apixaban, dabigatran, direct oral anticoagulant, edoxaban, rivaroxaban

scholarly journals Perioperative management of patients receiving non-vitamin K antagonist oral anticoagulants: up-to-date recommendations

2020 ◽  
Vol 15 (2) ◽  
pp. 133-142
Author(s):  
Kwang-Sub Kim ◽  
Jong Wook Song ◽  
Sarah Soh ◽  
Young-Lan Kwak ◽  
Jae-Kwang Shim
Keyword(s):  
Vitamin K ◽  
Clinical Evidence ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Vitamin K Antagonist ◽  
Thrombin Inhibitor ◽  
Reversal Agents ◽  
Perioperative Bleeding ◽  
Number Of Patients

Indications of non-vitamin K antagonist oral anticoagulants (NOACs), consisting of two types: direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitor (rivaroxaban, apixaban, and edoxaban), have expanded over the last few years. Accordingly, increasing number of patients presenting for surgery are being exposed to NOACs, despite the fact that NOACs are inevitably related to increased perioperative bleeding risk. This review article contains recent clinical evidence-based up-to-date recommendations to help set up a multidisciplinary management strategy to provide a safe perioperative milieu for patients receiving NOACs. In brief, despite the paucity of related clinical evidence, several key recommendations can be drawn based on the emerging clinical evidence, expert consensus, and predictable pharmacological properties of NOACs. In elective surgeries, it seems safe to perform high-bleeding risk surgeries 2 days after cessation of NOAC, regardless of the type of NOAC. Neuraxial anesthesia should be performed 3 days after cessation of NOACs. In both instances, dabigatran needs to be discontinued for an additional 1 or 2 days, depending on the decrease in renal function. NOACs do not require a preoperative heparin bridge therapy. Emergent or urgent surgeries should preferably be delayed for at least 12 h from the last NOAC intake (better if > 24 h). If surgery cannot be delayed, consider using specific reversal agents, which are idarucizumab for dabigatran and andexanet alfa for rivaroxaban, apixaban, and edoxaban. If these specific reversal agents are not available, consider using prothrombin complex concentrates.

Reversal of oral anticoagulants

ESC CardioMed ◽  
2018 ◽  
pp. 278-281
Author(s):  
Joanne van Ryn
Keyword(s):  
Clinical Trials ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Vitamin K Antagonist ◽  
Reversal Agent ◽  
Reversal Agents ◽  
Trial Testing

Oral anticoagulation reduces the risk of stroke in patients with atrial fibrillation and is effective in treating or preventing thromboembolic events. These indications have been the mainstay of vitamin K antagonist therapy for decades; however, in recent years a number of direct oral anticoagulants have also been approved for these indications. They circumvent many of the disadvantages associated with vitamin K antagonist use; however, the lack of a rapid and safe reversal strategy in emergency settings is often considered a hurdle to their more widespread use. Historically, coagulation factor concentrates have been used for rapid vitamin K antagonist reversal, though evidence from clinical trials has only been established in recent years. In addition, several new approaches to the specific reversal of anticoagulation have been developed. The first of these, idarucizumab, a specific reversal agent for dabigatran, was approved in 2015. A specific reversal agent for the factor Xa inhibitors, andexanet alfa, is currently in clinical trial testing, and a further compound, ciraparantag, is undergoing testing in healthy volunteers. This chapter discusses the mechanism of action of these reversal agents, their target anticoagulants, and the most recent data available in both volunteer and clinical trials.

scholarly journals Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis
Keyword(s):  
Side Effects ◽  
Intracranial Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Reversal Agents ◽  
United States Food ◽  
Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

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.

scholarly journals ORAL ANTICOAGULANTS IN THE TREATMENT OF VENOUS THROMBOEMBOLIC COMPLICATIONS: FOCUS ON APIXABAN

2017 ◽  
pp. 56-62 ◽  
Author(s):  
M. Yu. Gilyarov ◽  
E. V. Konstantinova
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Fixed Dose ◽  
Vein Thrombosis ◽  
Venous Thromboembolic ◽  
Deep Vein

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a common condition associated with a significant clinical and economic burden. Anticoagulant therapy is the mainstay of treatment for VTE. Current guidelines recommend the use of either low molecular weight heparins or fondaparinux overlapping with and followed by a vitamin K antagonist for the initial treatment of VTE, with the vitamin K antagonist continued when long-term anticoagulation is required. These traditional anticoagulants have practical limitations that have led to the development of direct oral anticoagulants that directly target either Factor Xa or thrombin and are administered at a fixed dose without the need for routine coagulation monitoring. The paper reviews results of the trials of apixaban application for treatment and/or long-term secondary prevention of VTE. The paper analyses effectiveness and safety of apixaban in different groups of patients, as well as features of apixaban application in every day practice.

scholarly journals Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Ali Zalpour ◽  
Thein Hlaing Oo
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Current Evidence ◽  
Thrombin Inhibitor ◽  
Prevention And Treatment ◽  
Financial Impacts

Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed.

scholarly journals Difficult Intraoperative Heparinization Following Andexanet Alfa Administration

2019 ◽  
Vol 3 (4) ◽  
pp. 390-394 ◽  
Author(s):  
C. James Watson ◽  
Sara Zettervall ◽  
Matthew Hall ◽  
Michael Ganetsky
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemodynamic Instability ◽  
The United States ◽  
Major Hemorrhage ◽  
Reversal Agents ◽  
Abdominal Aortic ◽  
United States Food ◽  
Andexanet Alfa

Direct oral anticoagulants are now commonplace, and reversal agents are recently becoming available. Andexanet alfa (AnXa), approved by the United States Food and Drug Administration in 2018, is a novel decoy molecule that reverses factor Xa inhibitors in patients with major hemorrhage. We present a case of a 70-year-old man taking rivaroxaban with hemodynamic instability from a ruptured abdominal aortic aneurysm. He received AnXa prior to endovascular surgery, and intraoperatively he could not be heparinized for graft placement. Consideration should be given to the risks and benefits of AnXa administration in patients who require anticoagulation after hemorrhage has been controlled.

scholarly journals The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 117S-126S ◽  
Author(s):  
Sariya Udayachalerm ◽  
Sasivimol Rattanasiri ◽  
Teeranan Angkananard ◽  
John Attia ◽  
Nakarin Sansanayudh ◽  
...  
Keyword(s):  
Case Reports ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitor ◽  
Aggregated Data ◽  
Reversal Agents ◽  
Death Studies ◽  
Risk Of Death

New oral anticoagulants (NOACs; ie, direct thrombin inhibitor [DTI] and factor Xa [FXa] inhibitors) were used as alternatives to warfarin. Specific antidotes (idarucizumab for dabigatran and andexanet alfa for FXa inhibitors) and hemostatic reversal agents were used for lowering bleeding, but their efficacies were still uncertain. The objectives of this study were to estimate and compare the efficacy of NOAC antidotes on bleeding reversal and death. Studies were identified from MEDLINE and Scopus databases until May 2018. Case reports/series and cohorts were selected if they assessed reversal or death rates. Data were independently extracted by 2 reviewers. Individual patient data and aggregated data of outcomes were extracted from case reports/series and cohorts. Binary regression was used to estimate outcome rates, risk ratio (RR) along with 95% confidence interval (CI). Interventions were NOACs and reversal agents (ie, DTI-specific, DTI-standard, FXa-specific, and FXa-standard). Among 220 patients of 93 case reports/series, reversal rates were 95.9%, 77.6%, and 71.5% for DTI-specific, FXa-standard, and DTI-standard. Pooled RRs for DTI-specific and FXa-standard versus DTI-standard, respectively, were 1.34 (CI: 1.13-1.60) and 1.09 (CI: 0.84-1.40). Death rate was 0.18 (CI: 0.06-0.57) times lower in DTI-specific versus DTI-standard. For pooling 10 subcohorts, pooled RRs were 1.08 (CI: 1.00-1.16), 1.29 (CI: 1.20-1.39), and 1.13 (CI: 1.01-1.25) for DTI-specific, FXa-specific, and FXa-standard versus DTI-standard. In conclusion, specific reversal agents might be useful for reversal of bleeding and lowering the risk of death than standard reversal agents. Our findings were based on case reports/series and selected cohorts, further comparative studies are thus needed.

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.

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