scholarly journals Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation: Pharmacology and Phase III Clinical Trials

10.5772/64440 ◽  
2016 ◽  
Author(s):  
Keval K. Patel ◽  
Ali A. Mehdirad ◽  
Richard Lee
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Phase Iii Clinical Trials

Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants

2015 ◽  
Vol 114 (12) ◽  
pp. 1113-1126 ◽  
Author(s):  
Charles V. Pollack ◽  
Jeffrey I. Weitz
Keyword(s):  
Clinical Trials ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Severe Bleeding ◽  
Reversal Agents ◽  
Phase Iii Clinical Trials ◽  
Meta Analyses

SummaryNon-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

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 Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

2016 ◽  
Vol 5 (2) ◽  
pp. 102 ◽  
Author(s):  
Marco Alings ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
The Other ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Efficacy And Safety ◽  
Pivotal Phase ◽  
Phase Iii Clinical Trials ◽  
Dosing Regimens

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACs: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACs offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACs should be considered in at-risk patient populations.

scholarly journals Stroke Prevention in Atrial Fibrillation

Circulation ◽  
2020 ◽  
Vol 142 (24) ◽  
pp. 2371-2388
Author(s):  
Aristeidis H Katsanos ◽  
Hooman Kamel ◽  
Jeff S. Healey ◽  
Robert G. Hart
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
High Risk ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Secondary Stroke Prevention

Ischemic strokes related to atrial fibrillation are highly prevalent, presenting with severe neurologic syndromes and associated with high risk of recurrence. Although advances have been made in both primary and secondary stroke prevention for patients with atrial fibrillation, the long-term risks for stroke recurrence and bleeding complications from antithrombotic treatment remain substantial. We summarize the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focus on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials. Non–vitamin K antagonist oral anticoagulants have been proven to be safer and equally effective compared with warfarin in stroke prevention for patients with nonvalvular atrial fibrillation. Non–vitamin K antagonist oral anticoagulants are being investigated for the treatment of patients with atrial fibrillation and rheumatic heart disease, for the treatment of patients with recent embolic stroke of undetermined source and indirect evidence of cardiac embolism, and in the prevention of vascular-mediated cognitive decline in patients with atrial fibrillation. Multiple clinical trials are assessing the optimal timing of non–vitamin K antagonist oral anticoagulant initiation after a recent ischemic stroke and the benefit:harm ratio of non–vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation and history of previous intracranial bleeding. Ongoing trials are addressing the usefulness of left atrial appendage occlusion in both primary and secondary stroke prevention for patients with atrial fibrillation, including those with high risk of bleeding. The additive value of prolonged cardiac monitoring for subclinical atrial fibrillation detection through smartphone applications or implantable cardiac devices, together with the optimal medical management of individuals with covert paroxysmal atrial fibrillation, is a topic of intensive research interest. Colchicine treatment and factor XIa inhibition constitute 2 novel pharmacologic approaches that might provide future treatment options in the secondary prevention of cardioembolic stroke attributable to atrial fibrillation.

scholarly journals DOACs vs Vitamin K Antagonists: a Comparison of Phase III Clinical Trials and a Prescriber Support Tool

2019 ◽  
Vol 7 (7) ◽  
pp. 1226-1232 ◽  
Author(s):  
Alina-Maria Pirlog ◽  
Cristian Daniel Pirlog ◽  
Marius Adrian Maghiar
Keyword(s):  
Clinical Trials ◽  
Vitamin K ◽  
Primary Outcome ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Phase Iii ◽  
Support Tool ◽  
Phase Iii Clinical Trials

AIM: The purpose of this article was to systematically review the literature assessing the efficacy and safety of phase III clinical trials for each direct oral anticoagulant versus vitamin K antagonists and to design a ’’go-to’’ table for the prescriber. MATERIAL AND METHODS: A systematic review of specialist literature was conducted to identify RCTs which compared direct oral anticoagulants (DOACs) with standard warfarin treatment. Medline, Em-base, and the Cochrane databases were searched from January 2005- January 2019. The inclusion criteria were randomised controlled trials of oral anticoagulants in patients with non-valvular atrial fibrillation (NVAF). Four publications were phase III randomised control trials (RCTs) included in the final analysis. RESULTS: Regarding the primary outcome in RELY the results were 1.69% per 100-year patients (p/y) for Warfarin compared to 1.11% p/y dabigatran etexilate 150mg BD (twice daily). In ROCKET AF the rates of the primary outcome were 2.2% p/y for warfarin compared to 1.7% p/y for rivaroxaban 20 mg OD (once daily). In ARISTOTLE trial the rates of the primary outcome were 1.60% p/y for warfarin compared to 1.27% p/y for apixaban 5 mg BD. In ENGAGE AF TIMI, the rates of the primary outcome were 1.50% p/y for warfarin compared to 1.18% p/y for edoxaban 60mg BD. CONCLUSION: DOACs showed to be either noninferior or superior to warfarin with regards to the primary outcome with better safety patterns. Our ’’go-to’’ table provides a supportive tool for physicians in preventing medical errors when managing patients on oral anticoagulants.

Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

2016 ◽  
Vol 5 (2) ◽  
pp. 1
Author(s):  
Marco Ailings ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
The Other ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Efficacy And Safety ◽  
Pivotal Phase ◽  
Phase Iii Clinical Trials ◽  
Dosing Regimens

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACs: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACs offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACs should be considered in at-risk patient populations.

scholarly journals The safety of new oral anticoagulants for ischemic stroke and systemic embolism prevention in females with atrial fibrillation

2021 ◽  
Vol 20 (1) ◽  
pp. 5-14
Author(s):  
Despina-Manuela Toader ◽  
◽  
Ileana Neaca ◽  
Alina Paraschiv ◽  
Rodica Musetescu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Factor X ◽  
Systemic Embolism

The prevalence of atrial fibrillation is lower in females than in men, but the risk of stroke and systemic thromboembolism is comparable or even higher. Administration of anticoagulant therapy does not modify this difference. Two classes of non-vitamin K antagonist oral anticoagulants were studied in atrial fibrillation: direct thrombin inhibitors, like Dabigatran, and activated factor X inhibitors, like Rivaroxaban, Apixaban and Edoxaban. Response to oral anticoagulants could differ between the gender. This medication was evaluated in phase III randomized controlled trials. Non-vitamin K antagonist oral anticoagulants have been proved more efficacious than Warfarin for stroke and systemic embolism prevention in women, but conclusions regarding the safety and the bleeding are heterogeneous. As in men, before prescribing a NOAC to a female with AF, the stroke and the bleeding risk have to be carefully estimated. It is important that future studies to be targeted on comparison between of non-vitamin K antagonist oral anticoagulants versus Warfarin in females with non-valvular atrial fibrillation.

Sign in / Sign up

Export Citation Format

Share Document