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

ABSTRACT: 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.

SUBMITTER: Mujer MTP

PROVIDER: S-EPMC7097770 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Mujer Mark Terence P MTP Rai Manoj P MP Atti Varunsiri V Dimaandal Ian Limuel IL Chan Abigail S AS Shrotriya Shiva S Gundabolu Krishna K Dhakal Prajwal P

Advances in hematology 20200127

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 ...[more]

PMID: 32231703

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Project description:BackgroundUse of the non-vitamin K antagonist oral anticoagulants (NOACs) is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF). However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA) of AF has not been well established yet.ObjectivesTo perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs) in patients undergoing RFCA.Data sourcesStudies were searched for in PubMed and Google Scholar databases.Study eligibility criteriaStudies were considered eligible if: they evaluated the clinical impact of NOACs versus VKAs; they specifically analyzed the use of anticoagulants during periprocedural phase of RFCA; they reported clinical outcome data.Study appraisal and synthesis methods25 studies were selected, including 9881 cases. The summary measure used was the risk ratio (RR) with 95% confidence interval (CI). The random-effects or the fixed effect model were used to synthesize results from the selected studies.ResultsThere was no significant difference in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001). Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41; p=0.01) events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).LimitationsAs with every meta-analysis, no patients-level data were available.Conclusions and implicationsThe use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no significant benefit on onset of thromboembolic events.

Project description:BackgroundWarfarin is a well-established agent for use in the prevention of stroke or systemic embolic event (SEE) in patients with nonvalvular atrial fibrillation (NVAF) and for the treatment of venous thromboembolism (VTE). However, management of patients requiring oral anticoagulation with warfarin can be complicated by the need for frequent monitoring, drug-drug and drug-food interactions, and a variable response based on genetic polymorphisms. The non-vitamin K antagonist oral anticoagulants (NOACs) were developed as alternatives to warfarin; they do not require routine monitoring and have predictable pharmacokinetics, fewer drug-drug interactions, and limited drug-food interactions. Four NOACs-dabigatran, rivaroxaban, apixaban, and edoxaban-have received approval from the US Food and Drug Administration for the prevention of stroke or SEE in NVAF and for the treatment of VTE. Selecting the most appropriate agent for each patient should be done in consideration of patient preferences and characteristics, including renal function, bleeding risk, and the need for other medications.MethodsA search was performed on the terms atrial fibrillation and venous thromboembolism with individual terms dabigatran, apixaban, edoxaban, or rivaroxaban to identify relevant manuscripts; large randomized clinical trials, metaanalyses, and treatment guideline recommendations were given preference. Searches to identify registries, treatment guidelines, and metaanalyses relevant to specific subgroups were also used.ResultsNOACs are effective in reducing the risk of stroke or SEE in patients with NVAF and are associated with fewer incidents of intracranial bleeding vs warfarin.ConclusionNOACs provide a convenient and safe alternative to warfarin and may result in improved therapeutic outcomes for patients with NVAF or VTE. The use of NOACs in other indications and patient populations is under investigation, and clinical trials investigating their use in acute coronary syndrome, medically ill patients, percutaneous coronary intervention, cardioversion, catheter ablation, coronary arterial disease, and heart failure have been announced.

Dataset Information

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

Publications

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

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