Convenient Anticoagulation Research Articles

Update on Management of Portal Vein Thrombosis and the Role of Novel Anticoagulants.

The clinical management of portal vein thrombosis (PVT) remains ambiguous due to its heterogeneous presentations and its associations with liver disease, malignancy, and hypercoagulable states. The natural history and clinical outcome of PVT are highly variable, dependent upon size, extent and degree of the thrombotic occlusion, as well as the physiological impact of patient comorbidities. While existing clinical guidelines consistently recommend low molecular weight heparin or vitamin K antagonist anticoagulation in cirrhotic patients with symptomatic acute PVT, management of asymptomatic and chronic PVT may need to be determined on a case-by-case basis, factoring in the state of underlying liver disease. In general, patients with PVT and underlying malignancy should be anticoagulated to alleviate symptoms and prevent recurrences that could disrupt the cancer management. However, existing clinical data does not support routine anticoagulation of cirrhotic patients with asymptomatic PVT in the absence of underlying cancer. While low molecular weight heparin and vitamin K antagonist remain the most commonly used agents in PVT, an emerging body of clinical evidence now suggests that direct-acting oral anticoagulants may be used safely and effectively in PVT. As such, direct-acting oral anticoagulants may offer a more convenient anticoagulation alternative for PVT management in future practice.

Abstract 11780: Temporal Trends, Racial and Gender Differences in the Use of Oral Anticoagulation in Medicare Patients With Newly Diagnosed Atrial Fibrillation

Introduction: The novel oral anticoagulants (NOAC’s) have provided convenient anticoagulation alternatives to warfarin for stroke prevention in atrial fibrillation (AF) patients. Hypothesis: We sought to study the temporal trends and racial/gender differences in the use of anticoagulants in AF patients from 2011 to 2013 in Medicare patients with newly diagnosed AF. Methods: Medicare claims from January 2010 to December 2013 were used to identify patients ≥66 years of age with newly diagnosed AF during 2011-2013, with no documented AF or anticoagulant use in the prior year. Race was identified from the Beneficiary Summary File. Data regarding initiation of oral anticoagulation within 90 days of AF diagnosis as well as type of anticoagulant were collected. We compared oral anticoagulant use for each year by race and sex. Results: Of the 755,079 patients with newly diagnosed AF, 85% were white, 6% were black, 5% were Hispanic and 4% were other non-white race. The mean age was 79 years and 58% were females. The proportion of patients receiving anticoagulation within 90 days of AF diagnosis decreased from 45% in 2011 to 40% in 2013. Overall, blacks and Hispanics were less frequently anticoagulated compared to whites (35%, 39% and 45% respectively). Females were also less likely to receive anticoagulation compared to males (45% versus 41% respectively). The use of NOAC’s increased from 27 % of patients who received anticoagulation in 2011 to 44% in 2013. Among anticoagulated patients, blacks and Hispanics were less likely to receive NOACs compared to whites (25% and 30% Vs 36%), and females compared to males (34% vs 36%). Conclusions: In this retrospective study of Medicare patients with newly diagnosed AF, we noted an increase in the use of NOAC’s from 2011 to 2013, but a decrease in the proportion of patients receiving anticoagulation. This highlights the importance of educating health care providers regarding AF and stroke prevention. Blacks or Hispanics and females were less likely to receive any anticoagulation or anticoagulation by an NOAC, compared to whites and males respectively.

Direct Oral Anticoagulants in Dental Patients Including the Frail Elderly Population.

Direct oral anticoagulants (DOACs) have led to a paradigm shift in the field of anticoagulation, providing safe and convenient anticoagulation without the need for regular blood testing. Currently, there are three major DOACs available—Factor Xa inhibitors (apixaban and rivaroxaban) and direct thrombin inhibitors (dabigatran)—that are available for use in atrial fibrillation and venous thromboembolism. While these agents have been shown to be as effective as warfarin, with a similar or better bleeding profile, there remains some concern of the use of these drugs in vulnerable populations, such as the frail elderly patients; particularly since reversal agents and drug monitoring are not routinely available. We aim to provide a review of the use of DOACs and the impact of DOACs on dental treatment in the elderly population.

Novel oral anticoagulants for the prevention of thromboembolism in patients with atrial fibrillation

The most significant complication of atrial fibrillation (AF) is thromboembolic stroke. Furthermore, the consequences of AF-related stroke tend to be more severe than those of other aetiologies. The need for safe, effective and convenient anticoagulation is clear. Warfarin is the current mainstay of treatment but its prescription and use remains sub-optimal, despite clear evidence and guidance to support its use. Many patients taking warfarin spend a significant amount of time subtherapeutically anticoagulated and the requirement for regular monitoring of warfarin's anticoagulant activity is both inconvenient and costly. Novel oral anticoagulants promise more predictable and convenient anticoagulation. They have potential superiority over warfarin for preventing thromboembolic stroke and appear to be associated with fewer haemorrhagic effects. Understanding the important background to the novel agents presents an opportunity to tailor anticoagulant treatment to the individual. This should allow a greater proportion of the eligible population access to effective anticoagulation. Furthermore, it should reduce their exposure to the risk of both thromboembolic and haemorrhagic stroke and their potentially devastating consequences.

Profilassi cardioembolica 2011: siamo vicini al tramonto del warfarin?

Warfarin has been the effective treatment in the prophylaxis of cardioembolism, in particular in patients with atrial fibrillation, for more than 50 years. Nevertheless, many patients with atrial fibrillation are not currently treated because of the numerous limits of oral anticoagulation and in those treated the quality of anticoagulation is often poor. Novel oral anticoagulant drugs, the direct thrombin antagonist dabigatran and factor Xa inhibitors such as rivaroxaban, apixaban, edoxaban, and betrixaban are more predictable and convenient anticoagulants in comparison with warfarin, mainly because of the non-requirement of regular laboratory monitoring and dose adjustments. Current data from phase III clinical trials are available for dabigatran, rivaroxaban and apixaban, which show to be at least noninferior in efficacy to warfarin for the prevention of stroke in patients with atrial fibrillation. This review focuses on the potential of novel anticoagulants to replace warfarin in patients with atrial fibrillation. Also the place in therapy and the potential limitations of the new agents in clinical practice represent important issues to be considered. The promise of new oral anticoagulants gives us the hope that warfarin will finally be replaced in a near future, but more importantly that anticoagulant undertreatment of atrial fibrillation will be partially overcome.

Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: Design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation–Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF–TIMI 48)

Vitamin K antagonists have been the standard oral antithrombotic used for more than a half century for prevention and treatment of thromboembolism. Their limitations include multiple food and drug interactions and need for frequent monitoring and dose adjustments. Edoxaban is a selective and direct factor Xa inhibitor that may provide effective, safe, and more convenient anticoagulation. ENGAGE AF-TIMI 48 is a phase 3, randomized, double-blind, double-dummy, multinational, noninferiority design megatrial comparing 2 exposure strategies of edoxaban to warfarin. Approximately 20,500 subjects will be randomized to edoxaban high exposure (60 mg daily, adjusted for drug clearance), edoxaban low exposure (30 mg daily, adjusted for drug clearance), or warfarin titrated to an international normalized ratio of 2.0 to 3.0. The edoxaban strategies provide for dynamic dose reductions in subjects with anticipated increased drug exposure. Blinded treatment is maintained through the use of sham international normalized ratios in patients receiving edoxaban. Eligibility criteria include electrical documentation of atrial fibrillation ≤12 months and a CHADS(2) score ≥2. Randomization is stratified by CHADS(2) score and anticipated drug exposure. The primary objective is to determine whether edoxaban is noninferior to warfarin for the prevention of stroke and systemic embolism. The primary safety end point is modified International Society on Thrombosis and Haemostasis major bleeding. Recruitment began in November 2008. The expected median follow-up is 24 months. ENGAGE AF-TIMI 48 is a phase 3 comparison of the novel oral factor Xa inhibitor edoxaban to warfarin for the prevention of thromboembolism in patients with atrial fibrillation.

Review: Will Warfarin Ever Be Replaced?

Arterial and venous thromboembolism account for significant morbidity and mortality worldwide. Warfarin, and other vitamin K antagonists (VKAs), have been the only class of oral anticoagulants currently in clinical use and have been so for over 50 years. Although warfarin is effective in preventing thromboembolism, its use is limited by its narrow therapeutic index that necessitates frequent monitoring and dose adjustments resulting in considerable inconvenience to patients and clinicians. There are now several orally administered anticoagulants in late stages of clinical development that may offer effective, safer, and more convenient anticoagulation. This review summarizes and compares data on novel anticoagulants in the prophylaxis and treatment of venous thromboembolism, acute coronary syndromes, and the prevention of stroke in patients with atrial fibrillation.

Adherence to a new oral anticoagulant treatment prescription: dabigatran etexilate

The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA) treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.

Prevention of Venous Thromboembolism after Total Hip Replacement with Once-Daily BAY 59-7939 - An Oral, Direct Factor Xa Inhibitor.

Venous thromboembolism is a serious risk after major surgery, and significant research is underway to develop novel, convenient anticoagulants. Patients undergoing hip replacement surgery are a suitable population for the study of novel anticoagulants because of a high rate of silent deep vein thromboses (DVTs), and the ability to quantify bleeding in a controlled environment. BAY 59-7939 is an oral, direct Factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. Dose-finding studies in hip and knee replacement patients showed that twice-daily, oral BAY 59-7939 initiated post-operatively had a wide therapeutic window, with similar efficacy and safety to enoxaparin (30 mg twice-daily or 40 mg once-daily) for the prevention of venous thromboembolism (VTE), and was unlikely to require monitoring. This European, randomized, double-blind, double-dummy, dose-finding study was performed to compare the efficacy and safety of once-daily, oral BAY 59-7939 with subcutaneous enoxaparin for VTE prevention in patients undergoing total hip replacement. Males over the age of 18 and postmenopausal females undergoing elective total hip replacement were randomized to oral BAY 59-7939 5, 10, 20, 30, or 40 mg once daily, or subcutaneous enoxaparin 40 mg once daily. Patients received enoxaparin on the evening before surgery and at least 6–8 hours after surgery, or BAY 59-7939 6–8 hours after surgery. Study drugs were then given every 24±2 hours. Each treatment group was to include 135 patients: a total of 810 patients. Mandatory bilateral ascending venography was performed 6–10 days after surgery; the last dose of study drug was given on the day before venography. Patients were followed for 30–60 days after the last study treatment. The primary efficacy endpoint was a composite of any DVT, objectively confirmed non-fatal pulmonary embolism (PE), and all-cause mortality; the secondary efficacy endpoint was major VTE - proximal DVT, PE, or VTE-related death. The primary safety endpoint was the incidence of major, post-operative bleeding not later than 2 days after the last intake of study drug; secondary safety endpoints included clinically relevant, non-major bleeding, and minor bleeding. An in-depth analysis of the study results will be presented here. Based on the study findings, the potential clinical impact of oral BAY 59-7939 administered once-daily for thromboprophylaxis in orthopaedic surgery will be discussed.

Direct thrombin inhibitors for anticoagulation.

To review the progress in developing direct thrombin inhibitors (DTIs) for anticoagulation within the context of existing anticoagulation therapies. Searches of MEDLINE (1993-June 2003) were conducted. We examined English-language articles, human studies, and relevant animal studies, and obtained additional citations from the references of these articles. Because of its pivotal role in hemostasis, thrombin is a key therapeutic target in the treatment and prevention of thromboembolic disorders. Conventional anticoagulant therapies, such as warfarin, unfractionated heparin, and low-molecular-weight heparin, exert their pharmacologic action by indirect thrombin inhibition. Although these agents are effective, each has limitations, prompting a search for more effective, specific, better-tolerated, and convenient anticoagulants. The efficacy and safety of factor Xa inhibitors are being investigated. Furthermore, the development of DTIs such as recombinant hirudin (lepirudin), bivalirudin, and argatroban continues. Challenges in the development of DTIs include establishing a binding affinity for thrombin that is not associated with excessive bleeding, attaining high thrombin specificity, achieving inhibition of both unbound and clot-bound thrombin, and producing an effective, fixed-dose oral anticoagulant to improve the practicality of anticoagulation therapy. Ximelagatran, an oral DTI designed to meet these standards, is currently in Phase III clinical trials. Significant progress has been made in developing DTIs. The recent emergence of orally administered DTIs may simplify the prevention and treatment of thrombosis.