scholarly journals Safety of a Four‐factor Prothrombin Complex Concentrate Versus Plasma for Vitamin K Antagonist Reversal: An Integrated Analysis of Two Phase III b Clinical Trials

2016 ◽  
Vol 23 (4) ◽  
pp. 466-475 ◽  
Author(s):  
Truman J. Milling ◽  
Majed A. Refaai ◽  
Ravi Sarode ◽  
Brandon Lewis ◽  
Antoinette Mangione ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Integrated Analysis ◽  
Two Phase

scholarly journals Four-Factor Prothrombin Complex Concentrate Reduces Time to Procedure in Vitamin K Antagonist-Treated Patients Experiencing Gastrointestinal Bleeding: A Post Hoc Analysis of Two Randomized Controlled Trials

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Majed A. Refaai ◽  
Truptesh H. Kothari ◽  
Shana Straub ◽  
Jacob Falcon ◽  
Ravi Sarode ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Invasive Procedure ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
The Impact

Introduction. To investigate the impact of a 4-factor prothrombin complex concentrate (4F-PCC [Beriplex®/Kcentra®]) versus plasma on “time to procedure” in patients with acute/severe gastrointestinal bleeding requiring rapid vitamin K antagonist (VKA) reversal prior to invasive procedure. Methods. A post hoc analysis of two phase III trials of 4F-PCC versus plasma in patients with acute/severe gastrointestinal bleeding. The treatment arms were compared for study treatment volume, infusion times, and time from start of study treatment to procedure. Results. Analysis included 42 patients (plasma, n=20; 4F-PCC, n=22). Median (interquartile range) infusion time was significantly shorter for the 4F-PCC group than for the plasma group (16 [13, 26] min versus 210 [149, 393] min; P<0.0001). Median infusion volumes were significantly smaller (103 [80, 130] mL versus 870 [748, 1001] mL; P<0.0001) and median time from study treatment initiation to first procedure was significantly shorter in the 4F-PCC group than in the plasma group (17.5 [12.8, 22.8] versus 23.9 [18.5, 62.0] h; P=0.037). Conclusions. In this analysis of patients with acute/severe gastrointestinal bleeding requiring urgent VKA reversal prior to an invasive procedure, 4F-PCC (compared with plasma) was associated with smaller infusion volumes, shorter infusion times, and reduced time to procedure.

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.

Anticoagulation strategies for venous thromboembolism: moving towards a personalised approach

2015 ◽  
Vol 114 (10) ◽  
pp. 660-669 ◽  
Author(s):  
Alexander Cohen ◽  
Stephen Black
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Clinical Outcomes ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Therapeutic Options ◽  
Phase Iii ◽  
Recent Position ◽  
Patient Subgroups

SummaryFour non-vitamin K antagonist oral anticoagulants (NOACs) have now been evaluated in clinical trials, providing new therapeutic options for the treatment of venous thromboembolism (VTE). Recent position statements call for a move towards tailored recommendations for the treatment of VTE, to better define in whom and under what conditions a particular anticoagulant may improve clinical outcomes. Here we review the phase III data on NOAC trials for the treatment of VTE, assessing the favourability of agents for particular patient subgroups and aetiologies. Where the data permit, individualised risks of recurrent VTE events and bleeding are presented.

Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy

2020 ◽  
pp. ejhpharm-2019-002114
Author(s):  
Carmen Sobrino Jiménez ◽  
José Antonio Romero-Garrido ◽  
Ángeles García-Martín ◽  
Manuel Quintana-Díaz ◽  
Carlos Jiménez-Vicente ◽  
...  
Keyword(s):  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonist ◽  
Fixed Dose ◽  
Dose Strategy

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.

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