Ximelagatran: A new type of oral anticoagulant

2005 ◽  
Vol 21 (4) ◽  
pp. 480-486
Author(s):  
Lisa Kwok ◽  
Dana Molckovsky ◽  
Michel Boucher
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Web Sites ◽  
Liver Toxicity ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Thrombin Inhibitors ◽  
Cochrane Library ◽  
Direct Thrombin Inhibitors ◽  
Elevated Liver Enzymes

Objectives: This assessment sought to evaluate the comparative benefit and adverse effect profile of ximelagatran, as well as the clinical issues surrounding its potential use.Methods: We performed a Dialog OneSearch across BIOSIS Previews, EMBASE, MEDLINE, PASCAL, and ToxFile to identify published literature. PubMed and The Cochrane Library were also searched. Gray literature was identified by searching a variety of Web sites of health technology assessment and related agencies and their associated databases. The manufacturer's Canadian office, AstraZeneca, was invited to submit information.Results: Ximelagatran is the first oral agent from a new class of anticoagulants called direct thrombin inhibitors. Other oral anticoagulants require routine blood monitoring; ximelagatran does not. Ximelagatran has been evaluated in the areas of venous thromboembolism management, particularly after orthopedic surgery, and stroke prevention in patients with atrial fibrillation. Overall, ximelagatran's efficacy appears comparable to other anticoagulants in these clinical settings. Also, bleeding rates were generally similar between ximelagatran and comparators but, as for warfarin, bleeding risk increases with higher ximelagatran doses. In addition, there is no specific antidote to help manage ximelagatran-induced bleeding. Finally, significantly more patients exposed to long-term ximelagatran developed elevated liver enzymes more than three times the upper normal limit, compared with patients on comparator anticoagulants.Conclusions: Given its apparent simplicity of use, ximelagatran carries the potential to replace, at least in part, anticoagulants currently used in the management of venous thromboembolism or for preventing stroke in atrial fibrillation patients. However, the safety of ximelagatran will not be fully known without further evaluation and surveillance for potential liver toxicity. There is also a need to evaluate its use in special populations such as patients with renal failure and patients using several concurrent medications.

Review of the Target-Specific Oral Anticoagulants in Development for the Treatment and Prevention of Venous Thromboembolism

2016 ◽  
Vol 29 (4) ◽  
pp. 392-405 ◽  
Author(s):  
Sandeep Devabhakthuni ◽  
Connie H. Yoon ◽  
Kathleen J. Pincus
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Decision Making ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Bleeding Risk ◽  
Clinical Decision ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Treatment And Prevention

Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism (VTE). Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists, limitations to their use still exists, leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors. To date, 3 target-specific oral anticoagulants (TSOACs) are Food and Drug Administration approved; several other agents are currently in development to optimize VTE management and minimize bleeding risks. The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE. Of the agents in development, edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents. Clinicians should understand the TSOACs under investigation, since differences in pharmacokinetics and pharmacodynamics may influence clinical decision making and agent selection for management of VTE. Currently, no direct comparisons between TSOACs have been conducted. Agents under investigation have yet to overcome the major limitations of the currently existing TSOACs. Further studies are necessary to clarify which TSOAC agent is best for management of VTE in clinical practice.

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.

Oral anticoagulants, effect on thrombus resolution and post-thrombotic syndrome

2016 ◽  
Vol 31 (1_suppl) ◽  
pp. 24-27
Author(s):  
Roger JMW Rennenberg
Keyword(s):  
Venous Thromboembolism ◽  
Medical Treatment ◽  
Oral Anticoagulants ◽  
Venous Blood ◽  
Thrombin Inhibitors ◽  
Cochrane Library ◽  
Clot Lysis ◽  
Direct Thrombin Inhibitors ◽  
Venous Blood Flow ◽  
Post Thrombotic Syndrome

Introduction Venous thromboembolism is a frequently occurring phenomenon with a high risk of acute and chronic complications. To prevent these, subjects are treated with surgical options to restore venous blood flow combined with medical treatment or medical treatment alone. Despite great therapeutic advances considerable morbidity still persists. For example, thrombosis of the leg can result in post-thrombotic syndrome, which has a great impact on quality of life. The best management to prevent the post-thrombotic syndrome is a topic of research and debate. In this study, we searched the literature to identify studies that used oral anticoagulants and evaluated their properties for resolution of thrombus and hence prevention of the post-thrombotic syndrome. Methods We searched PubMed, The Cochrane Library, and four international medical journals frequently reporting on venous thromboembolism. Furthermore, we looked at Clinicaltrials.gov for current research on this topic. Results Only three suitable articles were identified. Discussion We found experimental evidence that direct thrombin inhibitors and factor Xa inhibitors have an influence on clot lysis favoring a quicker recanalization compared to warfarin. Future studies investigating these effects in humans are warranted.

Spotlight on real-world evidence for the treatment of DVT: XALIA

2016 ◽  
Vol 116 (S 02) ◽  
pp. S41-S49 ◽  
Author(s):  
Alexander Turpie ◽  
Walter Ageno
Keyword(s):  
Venous Thromboembolism ◽  
Real World ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Standard Of Care ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Real World Evidence ◽  
Recurrent Vte

SummaryVenous thromboembolism (VTE), comprising both deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a serious and common cardiovascular disease associated with the risk of chronic complications, recurrent VTE events and even death. The treatment landscape has, in recent years, seen a paradigm shift from the use of traditional anticoagulants (low-molecular-weight heparin [LMWH] overlapping with and followed by a vitamin K antagonist [VKA]) to non-VKA oral anticoagulants (NOACs). This class of agents, encompassing direct factor Xa inhibitors and direct thrombin inhibitors have shown non-inferior efficacy and better safety to standard of care in randomised controlled trials (RCTs). The direct, oral factor Xa inhibitor rivaroxaban was the first to be approved for treatment of acute DVT and PE and secondary prevention of recurrent VTE events based on data from EINSTEIN DVT and EINSTEIN PE, respectively. Real-world evidence now helps to further support data from RCTs, and also bridges the gap for physicians regarding any areas of clinical uncertainty that may not be addressed by RCTs. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was the first large, prospective, observational, real-world study that has investigated the safety and effectiveness profile of rivaroxaban in patients with DVT and PE associated with DVT in routine clinical practice. This article will present the key clinical outcomes from this important global non-interventional study, and will discuss remaining questions to be addressed in Phase IV studies.

scholarly journals A REVIEW ON A COMPARATIVE STUDY ON EFFECTIVENESS AND SAFETY OF NOVEL ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Priyanka P K ◽  
Mathew George ◽  
Lincy Joseph
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Therapeutic Option ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Systemic Embolism ◽  
Anticoagulant Drugs

Atrial fibrillation (AF) is characterized as an extremely rapid and disorganized atrial activation. These irregular heartbeats will cause blood to collect within the heart and potentially form a clot, which can travel to a person’s brain and cause a stroke. AF increases stroke risk by 3 to 5 fold. Vitamin K antagonists (VKAs) are highly effective for the prevention of stroke, mainly of ischemic origin, in patients with AF. For this reason, VKAs are currently recommended in all AF patients at moderate to high risk for stroke or systemic embolism (SSE). VKAs have significant limitations, particularly their unpredictable anticoagulant response and numerous food and drug interactions, mandating regular laboratory monitoring. These limitations make treatment with VKAs problematic for many patients; as a result, only about half of all potentially eligible AF patients are treated with VKAs. Over the last several years, novel oral anticoagulant drugs (NOACs), including direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban & rivaroxaban), have been developed. New orally administered anticoagulant drugs have emerged as potential alternatives to VKAs for the prevention of ischaemic stroke or systemic embolism in patients with chronic atrial fibrillation. Novel oral anticoagulants (NOACs), due to their a lot of predictable therapeutic result and more favorable haemorrhagic risk profile, represent a particularly attractive therapeutic option in AF patients. Keywords:  Novel oral anticoagulants (NOACs), Vitamin K antagonist (VKAs), Atrial fibrillation, Apixaban, Dabigatran, Rivaroxaban.

scholarly journals Old and new oral anticoagulants for secondary stroke prevention in atrial fibrillation

2015 ◽  
Vol 9 (4) ◽  
pp. 314
Author(s):  
Tommaso Sacquegna ◽  
Anna Zaniboni ◽  
Andrea Rubboli ◽  
Gaetano Procaccianti ◽  
Michela Crisci ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Secondary Prevention ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Significant Difference

Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF), with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (<em>i.e</em>., dabigatran) and direct factor Xa inhibitors (<em>i.e</em>., apixaban and rivaroxaban) have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke) subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

scholarly journals A systematic review on the use of new anticoagulants in pregnancy

2013 ◽  
Vol 6 (2) ◽  
pp. 64-71 ◽  
Author(s):  
Ai-Wei Tang ◽  
Ian Greer
Keyword(s):  
Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Cochrane Library ◽  
Direct Thrombin Inhibitors ◽  
New Anticoagulants ◽  
Adverse Pregnancy ◽  
Newer Anticoagulants ◽  
The Cochrane Library ◽  
In Pregnancy

New anticoagulants such as direct factor Xa inhibitors and direct thrombin inhibitors have been recently developed, but their experience in pregnancy is limited. This review therefore aims to systematically search for studies on the use of these newer anticoagulants in pregnancy and the puerperal period. Searches were performed on electronic databases MEDLINE (from 1966), EMBASE (from 1974) and the Cochrane Library, until October 2011 using terms of ‘pregnancy’, ‘puerperium’, ‘breastfeeding’ and names of specific anticoagulants. The search yielded 561 citations and 11 studies (10 on fondaparinux, 1 on ximelagatran) were included. Newer anticoagulants (fondaparinux, hirudin and argatroban) on the limited evidence appear not to have adverse pregnancy outcomes, but there is currently no experience of new oral anticoagulants (rivaroxaban, apixaban, betrixaban or dabigatran) use in pregnancy. There is a need for reporting on new oral anticoagulation use in pregnancy to provide more information about the safety and risks to the fetus in utero.

scholarly journals Atrial Fibrillation: A Review of Recent Studies with a Focus on Those from the Duke Clinical Research Institute

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Meena P. Rao ◽  
Sean D. Pokorney ◽  
Christopher B. Granger
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
The United States ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Number Of Patients ◽  
Worse Prognosis ◽  
Research Institute

Atrial fibrillation is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States. The prevalence of atrial fibrillation averages 1% and increases with age. With the aging of the population, the number of patients with atrial fibrillation is expected to increase 150% by 2050, with more than 50% of atrial fibrillation patients being over the age of 80. This increasing burden of atrial fibrillation will lead to a higher incidence of stroke, as patients with atrial fibrillation have a five- to sevenfold greater risk of stroke than the general population. Strokes secondary to atrial fibrillation have a worse prognosis than in patients without atrial fibrillation. Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in atrial fibrillation. This review will summarize the experience of anticoagulants in patients with atrial fibrillation with a focus on the experience at the Duke Clinic Research Institute.

scholarly journals Prevention and Treatment of Venous Thromboembolism with New Oral Anticoagulants: A Practical Update for Clinicians

Thrombosis ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nay Min Tun ◽  
Thein Hlaing Oo
Keyword(s):  
Venous Thromboembolism ◽  
Patient Care ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Clinical Trial Data ◽  
Improve Patient Care ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Prevention And Treatment

Traditional anticoagulants, such as warfarin and enoxaparin, have several limitations, including parenteral administration, need for laboratory monitoring, and ongoing dose adjustment, which may limit optimal patient care. Newer oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban), have been developed to overcome these drawbacks, and thereby improve patient care. Several of these agents have been approved for use in the prevention and treatment of venous and/or systemic thromboembolism. The objective of this paper is to provide an overview of the available clinical trial data for these new oral anticoagulants in the prevention and treatment of venous thromboembolism and a practical update for clinicians.

scholarly journals New anticoagulants in the prevention and treatment of venous thromboembolism

2011 ◽  
Vol 152 (25) ◽  
pp. 983-992 ◽  
Author(s):  
Mátyás Keltai ◽  
Katalin Keltai
Keyword(s):  
Venous Thromboembolism ◽  
Treatment Options ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Current Treatment ◽  
Thrombin Inhibitors ◽  
Major Surgery ◽  
Direct Thrombin Inhibitors ◽  
New Anticoagulants ◽  
Prevention And Treatment

Clinical data on the risk factors, incidence, consequences and current treatment options of venous thromboembolism are reviewed. Current guidelines advise anticoagulant treatment for a few weeks or months in immobilized patients treated in hospital, and after major surgery. The initial treatment is based on heparin, followed by vitamin K antagonist treatment. Recently a number of new, partially orally administered medications have undergone clinical investigations and based on the results three of them were also registered for the prevention and treatment of venous thromboembolism. Direct thrombin inhibitors, direct and indirect Factor Xa inhibitors exhibited proven non-inferiority or superiority compared with traditional treatment options. The superior efficacy or non-inferiority was not accompanied with an increase in the bleeding risk. Results of the most important clinical trials are reviewed. Based on these results, prevention and treatment of venous thromboembolism will change substantially in the next future. Orv. Hetil., 2011, 152, 983–992.

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