scholarly journals An Update on the Reversal of Non-Vitamin K Antagonist Oral Anticoagulants

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Mark Terence P. Mujer ◽  
Manoj P. Rai ◽  
Varunsiri Atti ◽  
Ian Limuel Dimaandal ◽  
Abigail S. Chan ◽  
...  
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulants ◽  
Coagulation Factor ◽  
Heart Association ◽  
Vitamin K Antagonist ◽  
Thrombin Inhibitor ◽  
Minor Bleeding ◽  
Onset Of Action ◽  
Reversal Agents ◽  
Andexanet Alfa

Non-vitamin K antagonist oral anticoagulants (NOACs) include thrombin inhibitor dabigatran and coagulation factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban. NOACs have several benefits over warfarin, including faster time to the achieve effect, rapid onset of action, fewer documented food and drug interactions, lack of need for routine INR monitoring, and improved patient satisfaction. Local hemostatic measures, supportive care, and withholding the next NOAC dose are usually sufficient to achieve hemostasis among patients presenting with minor bleeding. The administration of reversal agents should be considered in patients on NOAC's with major bleeding manifestations (life-threatening bleeding, or major uncontrolled bleeding), or those who require rapid anticoagulant reversal for an emergent surgical procedure. The Food and Drug Administration (FDA) has approved two reversal agents for NOACs: idarucizumab for dabigatran and andexanet alfa for apixaban and rivaroxaban. The American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) have released an updated guideline for the management of patients with atrial fibrillation that provides indications for the use of these reversal agents. In addition, the final results of the ANNEXA-4 study that evaluated the efficacy and safety of andexanet alfa were recently published. Several agents are in different phases of clinical trials, and among them, ciraparantag has shown promising results. However, their higher cost and limited availability remains a concern. Here, we provide a brief review of the available reversal agents for NOACs (nonspecific and specific), recent updates on reversal strategies, lab parameters (including point-of-care tests), NOAC resumption, and agents in development.

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.

Perioperative Management of Patients Receiving New Anticoagulants

2019 ◽  
Vol 25 (19) ◽  
pp. 2149-2157 ◽  
Author(s):  
Massimo Lamperti ◽  
Andrey Khozenko ◽  
Arun Kumar
Keyword(s):  
Vitamin K ◽  
Elective Surgery ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Oral Intake ◽  
Bleeding Risk ◽  
Dietary Vitamin ◽  
Reversal Agent ◽  
Onset Of Action ◽  
Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

2020 ◽  
Vol 73 (11) ◽  
pp. 2528-2534
Author(s):  
Dagmara Wojtowicz ◽  
Anna Tomaszuk-Kazberuk ◽  
Jolanta Małyszko ◽  
Marek Koziński
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Anticoagulant Activity ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Reversal Agents ◽  
Limited Availability ◽  
Increased Risk

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.

Reversal agents for non-vitamin K antagonist oral anticoagulants

2018 ◽  
Vol 15 (5) ◽  
pp. 273-281 ◽  
Author(s):  
Jerrold H. Levy ◽  
James Douketis ◽  
Jeffrey I. Weitz
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Reversal Agents

scholarly journals Patients Taking Direct Oral Anticoagulants (DOAC) Undergoing Oral Surgery: A Review of the Literature and a Proposal of a Peri-Operative Management Protocol

Healthcare ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 281
Author(s):  
Saturnino Marco Lupi ◽  
Arianna Rodriguez y Baena
Keyword(s):  
Vitamin K ◽  
Oral Surgery ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Thrombin Inhibitor ◽  
Review Of The Literature ◽  
Risk Of Bleeding ◽  
Management Protocol ◽  
Increased Risk

Patients on anticoagulant therapy for the prevention of cardiovascular accidents present an increased risk of bleeding following dental and oral surgery. Four recently introduced non-vitamin K antagonist oral anticoagulants, namely dabigatran etexilate (direct thrombin inhibitor), rivaroxaban, apixaban, and edoxaban (Xa factor direct inhibitor), are widely spreading for convenience of use compared to the older drug class. Dental management of patients taking these drugs has substantial differences compared to patients on vitamin K antagonist therapy. Anticoagulation is not assessed directly through a hematological test, but indirectly by renal function. The interventions must be scheduled at the time of minimum blood concentration of the drug. Bleeding can occur even after several days following the surgery. The interaction with drugs administered for dental care must be carefully evaluated. The peri-operative diet can influence the risk of bleeding. Local measures favoring coagulation must be adopted. The interventions with higher risk must be divided into multiple less invasive interventions. Although antidotes exist for these drugs, their use does not seem necessary for dental interventions that have been planned optimally. Furthermore, in this review of the literature a decision protocol is proposed for the evaluation of the suspension of the anticoagulant drug before oral surgery. Cessation of any anticoagulant should only be made in consultation with the patient’s general practitioner/cardiologist, who will weigh up the risk of bleeding from the proposed procedure with the risk of thrombosis/stroke in each individual patient.

Problem-Based Review: Non Vitamin K Antagonist Oral Anticoagulants for the Acute Physician

2015 ◽  
Vol 14 (2) ◽  
pp. 83-89
Author(s):  
Jecko Thachil ◽  
◽  
James Gagg ◽  
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Rapid Onset ◽  
Vitamin K Antagonist ◽  
Thrombin Inhibitor ◽  
Oral Formulations ◽  
Direct Anticoagulants ◽  
And Function

Non-vitamin K antagonist oral anticoagulants (NOACs), are direct anticoagulants which inhibit specific coagulation factors and function as anticoagulants. Three NOACs are currently licensed in the United Kingdom: dabigatran, a thrombin inhibitor, and rivaroxaban and apixaban, antagonists of factor Xa. They are set to change the anticoagulant landscape, which was previously ruled by warfarin and heparins. Their advantages including oral formulations, rapid onset and offset of action, predictable pharmacokinetics, no requirement for routine blood monitoring or dose adjustment and very few drug interactions. The increasing use of these drugs means the acute medicine physicians are likely to encounter patients who have been taking them. This article reviews some of the challenging clinical situations in which this may arise.

scholarly journals Direct-Acting Oral Anticoagulants and Their Reversal Agents—An Update

Medicines ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 103 ◽  
Author(s):  
Stephanie Kustos ◽  
Pius Fasinu
Keyword(s):  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Rapid Onset ◽  
Thrombin Inhibitor ◽  
Reversal Agent ◽  
Onset Of Action ◽  
Reversal Agents ◽  
Direct Acting ◽  
Direct Acting Oral Anticoagulants

Background: Over the last ten years, a new class of drugs, known as the direct-acting oral anticoagulants (DOACs), have emerged at the forefront of anticoagulation therapy. Like the older generation anticoagulants, DOACs require specific reversal agents in cases of life-threatening bleeding or the need for high-risk surgery. Methods: Published literature was searched, and information extracted to provide an update on DOACS and their reversal agents. Results: The DOACs include the direct thrombin inhibitor—dabigatran, and the factor Xa inhibitors—rivaroxaban, apixaban, edoxaban, and betrixaban. These DOACs all have a rapid onset of action and each has a predictable therapeutic response requiring no monitoring, unlike the older anticoagulants, such as warfarin. Two reversal agents have been approved within the last five years: idarucizumab for the reversal of dabigatran, and andexanet alfa for the reversal of rivaroxaban and apixaban. Additionally, ciraparantag, a potential “universal” reversal agent, is currently under clinical development. Conclusions: A new generation of anticoagulants, the DOACs, and their reversal agents, are gaining prominence in clinical practice, having demonstrated superior efficacy and safety profiles. They are poised to replace traditional anticoagulants including warfarin.

Use of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients with Malignancy: Clinical Practice Experience in a Single Institution and Literature Review

2017 ◽  
Vol 44 (04) ◽  
pp. 370-376 ◽  
Author(s):  
Anna Rago ◽  
Andrea Papa ◽  
Federica Meo ◽  
Emilio Attena ◽  
Paolo Golino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Cardiovascular Complications ◽  
Vitamin K Antagonist ◽  
Minor Bleeding ◽  
Bleeding Events ◽  
Study Population ◽  
Ischemic Attack

AbstractThis observational study aimed to investigate the efficacy and safety of non–vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with malignancy. A total of 76 patients (mean age: 73.2 ± 8.9; 28 females) with AF and malignancy treated with NOAC were included in the analysis. The mean CHA2DS2-VASc and HAS-BLED scores were 3.2 ± 1.2 and 2.2 ± 0.9, respectively. The study population was taking dabigatran 150 mg (25%) twice daily (BID), apixaban 5 mg BID (25%), dabigatran 110 mg BID (24%), rivaroxaban 20 mg (18%) once a day (OD), rivaroxaban 15 mg OD (5%), or apixaban 2.5 mg OD (3%). NOAC therapy began, on average, 248 ± 238 days before malignancy diagnosis for an average duration of 1,000 ± 289 days. Stroke, transient ischemic attack, major and minor bleeding events, other adverse effects, and major cardiovascular complications during the follow-up period were collected. In our study population, no patients experienced thromboembolic events during therapy with any NOAC. We recorded a low global incidence of major bleeding (3.9%) with a mean annual incidence of 1.4%. No hemorrhagic stroke or subarachnoid hemorrhage was observed. Only nine patients (11.8%) experienced minor bleeding. According to our data, anticoagulation therapy with NOACs seems to be an effective and safe treatment strategy for nonvalvular AF patients with malignancy.

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