New oral anticoagulants.
Ontology highlight
ABSTRACT:
SUBMITTER: Sun D
PROVIDER: S-EPMC3589329 | biostudies-literature | 2013 Mar
REPOSITORIES: biostudies-literature
Publications
New oral anticoagulants.
Sun Dongmei D Lazo-Langner Alejandro A
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20121112 4
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Project description:The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk-benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs. However, both dabigatran 150 twice daily and rivaroxaban have a slightly higher incidence of gastrointestinal bleeding when compared with VKAs. The article will delineate the current knowledge as well as scientific gaps related to the choice and dosage of anticoagulation regimens for various NVAF subsets and will address certain common clinical scenarios requiring special considerations. The article also addresses the shortcomings of NOACs: lack of therapeutic pharmacokinetic and pharmacodynamic targets, absence of tools to assess compliance and efficacy, rigid and limited dosage options, and absence of effective and inexpensive reversal agents.
| S-EPMC6490750 | biostudies-literature
Project description:INTRODUCTION: Patients undergoing elective total hip or total knee replacement surgery are at increased risk of venous thromboembolism in the post-operative period and are recommended to receive thromboprophylaxis for 10-35 days. Although several thromboprophylactic agents are available, these are associated with well-recognized limitations. For the low molecular weight heparins (LMWHs) such as enoxaparin, these limitations include parenteral administration, indirect mode of action, inability to inhibit clot-bound thrombin and association with complications such as heparin-induced thrombocytopenia. These limitations make post-operative thromboprophylaxis challenging. Several new oral anticoagulants are in the advanced stages of clinical development. These agents have been designed to target either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban), which are key coagulation cascade enzymes. METHODS AND RESULTS: This review will present the published phase III clinical trial evidence of the efficacy and safety of dabigatran etexilate, rivaroxaban and apixaban, compared with the LMWH enoxaparin for the prevention of venous thromboembolism in patients who have undergone elective total hip or total knee replacement surgery. All three agents have shown comparable or superior efficacy compared with the European dose regimen of enoxaparin (40 mg once daily), and comparable rates of major bleeding events. Dabigatran etexilate and rivaroxaban are currently licensed for use following elective hip and knee replacement surgery in many countries, but no direct comparative data exist upon which to base the choice of agent. CONCLUSION: A thorough assessment of each individual patient's thromboembolic and bleeding risks should be the basis of selecting the agent in order to balance efficacy and safety.
| S-EPMC3150805 | biostudies-literature
Project description:Venous thromboembolism (VTE) is associated with increased morbidity and mortality, decreased quality of life, and higher economic burden in patients with cancer. Currently, the treatment of VTE in patients with cancer is particularly challenging. For many years, low molecular weight heparin (LMWHs) has been the standard for the treatment of cancer-associated VTE. Recently, the introduction of new oral anticoagulants (NOACs) may offer an oral anticoagulant option for some patients with cancer-associated thrombosis (CAT) as a growing body of literature supports the use of NOACs in the setting of CAT. With the use of NOAC as a new option in the management of CAT, clinicians now face several choices for the individual cancer patient with VTE. We need a more in-depth understanding of the drug properties, efficacy and safety, economic analysis that allows us to choose the most appropriate treatment for each patient. In the review, we will present an overview of CAT management, discuss the available evidence, economic costs for NOACs in the treatment of CAT, and seek to provide the best range of treatments for cancer patients.
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Project description:Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in this rapidly aging society.
| S-EPMC4060270 | biostudies-literature
Project description:Guidelines published by the British Society of Gastroenterology have standardised the care of patients attending for endoscopy procedures, taking aspirin, clopidogrel and warfarin. Two new oral anticoagulant drugs, Rivaroxaban and Dabigatran, are licensed and National Institute of Clinical Excellence (NICE) approved for use in the UK. Unlike warfarin, these drugs do not require regular monitoring, and are at least as effective in preventing stroke in non-valvular atrial fibrillation. As such, they are likely to become popular among patients and clinicians alike. This paper summarises the practical management of patients taking these drugs attending for endoscopic procedures.
| S-EPMC5369837 | biostudies-other
Project description:About 1.4 British million people are at risk of strokes due to non-valvular atrial fibrillation (AF) necessitating long-term anticoagulation. The vitamin K antagonist, warfarin, has a long half-life and narrow therapeutic range necessitating regular monitoring and is a common cause of iatrogenic hospital admission. Direct-acting oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban are not required to have monitoring but are sensitive to changes in renal function and are associated with poorer adherence. There are good grounds to believe that DOACs are not always superior to warfarin in routine practice particularly with an older population. Much higher levels of therapeutic effectiveness can be achieved using a simple genotype guidance to identify those who are highly sensitive and by adoption of home monitoring. These adjustments could make warfarin the preferred drug for most people and would reduce the dramatic rise in health service expenditure.
| S-EPMC5845414 | biostudies-literature
Project description:Reversal agents for direct oral anticoagulants (DOACs), including factor X inhibitors and direct thrombin inhibitors, are a major concern in clinical practice. After DOACs were introduced and became widely used as an alternative for vitamin K antagonists in the management of venous thromboembolism and nonvalvular atrial fibrillation, the need for effective reversal agents has increased, particularly for life-threatening bleeding episodes related to DOACs or to reverse medication effects during urgent interventions. In the absence of specific reversal agents, prothrombin complex concentrate (PCC) and activated PCC are reasonable options to reverse bleeding associated with DOACs. However, high-quality clinical evidence is lacking. Idarucizumab is the only agent approved by the US Food and Drug Administration to reverse the effects of dabigatran; andexanet alfa and ciraparantag are also under evaluation as reversal agents for DOACs. This review summarizes the current evidence for nonspecific and specific reversal of DOACs.
| S-EPMC5529093 | biostudies-other
Project description:New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.
| S-EPMC8282556 | biostudies-literature
Project description:BackgroundDabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons.Methods and resultsWe included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban.ConclusionsAn indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
| S-EPMC3471365 | biostudies-literature
Project description:BackgroundDetermination of anticoagulant therapy is of pronounced interest in emergency situations. However, routine tests do not provide sufficient insight. This study was performed to investigate the impact of anticoagulants on the results of viscoelastometric assays using the ClotPro device.MethodsThis prospective, observational study was conducted in patients receiving dabigatran, factor Xa (FXa)-inhibitors, phenprocoumon, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) (local ethics committee approval number: 17-525-4). Healthy volunteers served as controls. Viscoelastometric assays were performed, including the extrinsic test (EX-test), intrinsic test (IN-test) Russel's viper venom test (RVV-test), ecarin test (ECA-test), and the tissue plasminogen activator test (TPA-test).Results70 patients and 10 healthy volunteers were recruited. Clotting time in the EX-test (CTEX-test) was significantly prolonged versus controls by dabigatran, FXa inhibitors and phenprocoumon. CTIN-test was prolonged by dabigatran, FXa inhibitors and UFH. Dabigatran, FXa inhibitors and UFH significantly prolonged CTRVV-test in comparison with controls (median 200, 207 and 289 vs 63 s, respectively; all p < 0.0005). Only dabigatran elicited a significant increase in CTECA-test compared to controls (median 307 vs 73 s; p < 0.0001). CTECA-test correlated strongly with dabigatran plasma concentration (measured by anti-IIa activity; r = 0.9970; p < 0.0001) and provided 100% sensitivity and 100% specificity for detecting dabigatran. Plasma concentrations (anti-XA activity) of FXa inhibitors correlated with CTRVV-test (r = 0.7998; p < 0.0001), and CTRVV-test provided 83% sensitivity and 64% specificity for detecting FXa inhibitors.ConclusionsIn emergency situations, ClotPro viscoelastometric assessment of whole-blood samples may help towards determining the presence and type of anticoagulant class that a patient is taking.Trial registrationGerman clinical trials database ID: DRKS00015302 .
| S-EPMC7962229 | biostudies-literature