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1.
Direct oral anticoagulants for extended treatment of venous thromboembolism: insights from the EINSTEIN CHOICE study.
Imberti, D, Pomero, F, Mastroiacovo, D
Blood transfusion = Trasfusione del sangue. 2020;(1):49-57
Abstract
The risk of recurrence of venous thromboembolism (VTE) persists after interruption of the initial anticoagulation therapy. New evidence shows that direct oral anticoagulants are effective for extended treatment of VTE and may reduce the risk of all-cause mortality. The optimal duration of anticoagulation after VTE is, however, controversial and complicated by the need for individualised assessment and balance between thrombosis and bleeding risks. Three direct oral anticoagulants (rivaroxaban, apixaban and dabigatran) have been studied for extended treatment of VTE. Dabigatran was shown to be safer than vitamin K antagonists and similarly effective for the prevention of recurrent VTE. Dabigatran, apixaban and rivaroxaban resulted in significant decreases in the rate of recurrent symptomatic VTE when compared to placebo, without a statistically significant difference in the risk of major bleeding. The latest guidelines of the American College of Chest Physicians suggest the use of low-dose aspirin to prevent VTE recurrence in patients who want to stop anticoagulation. In the randomised, double-blind, phase 3 EINSTEIN CHOICE trial, once-daily rivaroxaban at doses of 20 mg or 10 mg and 100 mg of aspirin were compared in VTE patients for whom there was clinical equipoise for extended anticoagulation. Either a treatment dose (20 mg) or a prophylactic dose (10 mg) of rivaroxaban significantly reduced the risk of VTE recurrence without a significant increase in bleeding risk compared with aspirin. The EINSTEIN CHOICE trial included patients with provoked or unprovoked VTE. Patients with VTE provoked by minor persistent or minor transient risk factors enrolled in this trial had not-negligible VTE recurrence rates. These new findings on extended therapy suggest the possibility of anticoagulation regimens at intensities tailored to the patients' risk profiles and VTE characteristics, with a shift of the risk-benefit balance in favour of extended treatment.
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2.
Bleeding in anticoagulated patients with atrial fibrillation: practical considerations.
Undas, A, Drabik, L, Potpara, T
Polish archives of internal medicine. 2020;(1):47-58
Abstract
Major bleeding (especially intracranial hemorrhage) is the most feared adverse event observed in patients with atrial fibrillation (AF) receiving oral anticoagulation. Clinical risk factor-based scores have modest ability to predict major or clinically relevant bleeds, and blood biomarkers are increasingly implemented to improve bleeding prognostication in patients with AF on life‑long anticoagulation. To improve the safety of anticoagulation in the era of non-vitamin K antagonist oral anticoagulants (NOACs, or direct oral anticoagulants [DOACs], including dabigatran, rivaroxaban, apixaban, and edoxaban), specific demographic, clinical, and laboratory variables should be considered. The current review summarizes practical challenges in the management of oral anticoagulation with emphasis on the risk assessment tools, elderly or underweight patients, cancer patients, impact of chronic kidney disease, liver cirrhosis, and thrombocytopenia in the context of bleeding risk in patients with AF.
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3.
A rapid evidence assessment of bleed-related healthcare resource utilization in publications reporting the use of direct oral anticoagulants for non-valvular atrial fibrillation.
Shah, BR, Scholtus, E, Rolland, C, Batscheider, A, Katz, JN, Nilsson, KR
Current medical research and opinion. 2019;(1):127-139
Abstract
Objective: Non-valvular atrial fibrillation (NVAF), a common cardiac arrhythmia, is associated with high morbidity and carries a substantial economic burden. Historically, vitamin K antagonists (VKAs; e.g. warfarin) have been used for therapy of NVAF, but recently several direct oral anticoagulants (DOACs) have been approved for prevention of stroke in patients with NVAF. This review summarizes the real-world evidence (RWE) for healthcare resource utilization (HRU) in patients receiving oral anticoagulants (VKAs and/or DOACs) for therapy of NVAF.Methods: A PRISMA-compliant literature search assessed Medline® and Embase® databases from 1 January 2011 to 4 May 2017, and the National Health Service Economic Evaluation Database from 1 January 2011 to 31 December 2015. Publications were included if they reported observational data from real-world use of one or more anticoagulant therapies. Outcomes of interest included hospitalizations, length of stay (LOS), mortality and costs.Results: Twenty-eight publications were included. Apixaban and dabigatran were associated with fewer bleed-related hospitalizations than warfarin. Bleed-related LOS were generally longer for warfarin than for DOACs. Bleed-related treatment costs were lower for patients receiving apixaban or receiving dabigatran than patients receiving rivaroxaban or receiving warfarin. Bleed-related mortality in patients receiving oral anticoagulation for treatment of NVAF were low across all DOACs and warfarin.Conclusions: The limited available evidence for HRU burden among patients receiving oral anticoagulation for NVAF suggests that DOACs (particularly apixaban and dabigatran) offer some degree of benefit in terms of HRU outcomes, compared with warfarin. Further work is required to understand HRU outcomes in patients receiving DOACs.
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4.
Direct-Acting Oral Anticoagulants in Critically Ill Patients.
Rali, P, Gangemi, A, Moores, A, Mohrien, K, Moores, L
Chest. 2019;(3):604-618
Abstract
The direct-acting oral anticoagulants (DOACs) have been increasingly used over vitamin K antagonists in recent years because they do not require monitoring and have an immediate anticoagulation effect. In general, DOACs have exhibited a better safety profile and noninferiority for prophylaxis and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation compared with vitamin K antagonists in the non-ICU population; whether this finding holds true in patients who are critically ill remains unknown. The current review addresses the role of DOACs in special ICU populations, use of these agents for VTE prophylaxis, perioperative management of DOACs, drug monitoring, and potential drug interactions of DOACs in critically ill patients. Adverse events and available reversal agents for DOACs are also discussed.
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5.
To Maintain or Cease Non-Vitamin K Antagonist Oral Anticoagulants Prior to Minimal Bleeding Risk Procedures: A Review of Evidence and Recommendations.
Brennan, Y, Favaloro, EJ, Curnow, J
Seminars in thrombosis and hemostasis. 2019;(2):171-179
Abstract
For procedures associated with minimal bleeding risk, there are data and experience to support the practice of continuing vitamin K antagonists rather than interrupting therapy, to prevent exposing patients to the undue risk of developing thromboembolism during anticoagulation cessation. Despite the increasing use of non-vitamin K oral anticoagulants (NOACs), there is little evidence to guide the management of these drugs around minimal bleeding risk procedures. This review examines and discusses the major society guidelines and recommendations addressing the management of NOACs around minimal bleeding risk procedures. Additionally, it summarizes the existing evidence, and highlights the gaps in knowledge where evidence is not yet available. Finally, recommendations are made to assist the proceduralist deal with this area of limited evidence.
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6.
Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Vitamin K Antagonist Reversal: Does One Dose Fit All?
Schwebach, AA, Waybright, RA, Johnson, TJ
Pharmacotherapy. 2019;(5):599-608
Abstract
Four-factor prothrombin complex concentrate (4F-PCC) has emerged as the preferred option for emergent reversal of vitamin K antagonists (VKAs); however, the optimal dosing strategy is unknown. Although several studies have attempted to determine the optimal dose of 4F-PCC using a variety of dosing regimens, no dosing strategy has been found to be superior. Many of these studies have evaluated a low, fixed dose of 4F-PCC rather than individualized dosing as recommended in product labeling. The purpose of this review was to evaluate the efficacy and safety of various fixed-dose strategies of 4F-PCC for emergent VKA reversal and to assess limitations of the existing literature. A search of the PubMed database was performed from the earliest available date through 2018 for relevant articles describing fixed-dose 4F-PCC for VKA reversal. Reference lists of relevant articles were also manually reviewed. Most currently available studies are primarily observational and heterogeneous in design. A very low fixed dose of 500 IU is likely inadequate for successful VKA reversal, but increased fixed doses of 1000-1500 IU have found some degree of success and may be considered for VKA reversal. However, many of these studies consistently identified a trend toward international normalized ratio (INR) reversal failure in patients presenting with high baseline INR values or intracranial hemorrhage, suggesting that higher 4F-PCC doses are needed in these patients. Available studies are underpowered to determine whether a dose-dependent association with thrombotic risk exists. Additional large, randomized studies are needed to determine the optimal dosing strategy and ascertain the role for fixed-dose 4F-PCC.
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7.
Stroke Prevention, Evaluation of Bleeding Risk, and Anticoagulant Treatment Management in Atrial Fibrillation Contemporary International Guidelines.
Proietti, M, Lane, DA, Boriani, G, Lip, GYH
The Canadian journal of cardiology. 2019;(5):619-633
Abstract
In recent years the management of atrial fibrillation patients has progressively and substantially changed because of the introduction of new treatments and the availability of new data regarding the epidemiology and clinical management of these patients. In the past 2 years alone, there have been 7 new guidelines or guideline updates that have been published, which have introduced new recommendations and significantly revised previously published ones. Two updates for Canadian guidelines were published in 2016 and 2018, whereas guidelines from the European Society of Cardiology in 2016, Asia Pacific Heart Rhythm Society were published in 2017, National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand, American College of Chest Physicians, and Korean Heart Rhythm Society have been published in 2018. In this narrative review we provide a comparison of these contemporary international guidelines, with particular attention on the evaluation of thromboembolic and bleeding risks and management of oral anticoagulant therapy. From the analysis of contemporary guidelines on the management of atrial fibrillation, a general agreement is evident about the baseline evaluation of thromboembolic and bleeding risk, as well as a preference for the use of non-vitamin K antagonist oral anticoagulants. Also, regarding the concomitant use of oral anticoagulant and antiplatelet drugs in patients with acute coronary syndromes, undergoing elective percutaneous coronary intervention, catheter ablation, and cardioversion procedures, all of the guidelines agree on the general principles and are supported by evidence. More data are still needed to better substantiate recommendations for specific atrial fibrillation subpopulations. The need for an integrated approach and holistic management is highlighted in the more recently published guidelines.
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8.
An update on the new classification of Ehlers-Danlos syndrome and review of the causes of bleeding in this population.
Jesudas, R, Chaudhury, A, Laukaitis, CM
Haemophilia : the official journal of the World Federation of Hemophilia. 2019;(4):558-566
Abstract
It has long been hypothesized that bleeding symptoms in people with hypermobility occur as a result of abnormalities in the collagen of the vessel wall or the connective tissues. The bleeding symptoms, particularly in the skin, have been attributed to the fragility of skin and blood vessels caused by "defective collagen wickerwork" of the reticular layer of the skin. Collagen, which forms the framework of vessel walls, is altered in many patients with Ehlers-Danlos syndrome (EDS) leading to weakening of the vessel wall or the supporting tissues. Another important function of subendothelial collagen is its interaction with platelets and von Willebrand factor, which results in the propagation of a platelet plug. Thus, abnormalities in subendothelial collagen may alter its interaction with platelets and VWF. More recently, hypermobile-EDS (hEDS) has been associated with mast cell disorders, a condition independently associated with bleeding symptoms. It has also been observed that patients with mild bleeding disorders have a more severe bleeding phenotype when they have co-existing joint hypermobility.
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9.
Antithromboembolic Strategies for Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.
Ather, A, Laliberte, B, Reed, BN, Schenk, A, Watson, K, Devabhakthuni, S, See, VY
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2018;(6):441-455
Abstract
We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6-12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y12 inhibitor used. Each category review was followed by a discussion providing insight into the quality of evidence and implications for practice. We found that the risk of bleeding with TT was higher than with DT, without demonstrated added benefit of reducing major adverse cardiovascular events. TT use should be minimized in patients with high bleeding risk, and patient-specific factors should be critically analyzed to select appropriate antiplatelet and anticoagulant agents.
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10.
Hemostasis in the Very Young.
Kenet, G, Barg, AA, Nowak-Göttl, U
Seminars in thrombosis and hemostasis. 2018;(7):617-623
Abstract
Hemostasis is a dynamic process that starts in utero. The coagulation system evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins in early life compared with adulthood. This concept, known as "developmental hemostasis," has important biological and clinical implications. Overall, impaired platelet function, along with physiologically reduced levels of vitamin K-dependent and contact coagulation factors, may cause poorer clot firmness even in healthy neonates. However, increased activity of von Willebrand factor and low levels of coagulation inhibitors that promote hemostasis counterbalance the delicate and immature hemostatic system. Since this hemostatic system has little reserve capacity, preterm neonates or sick infants are extremely vulnerable and predisposed to either hemorrhagic or thrombotic complications. This review will address the concept and manifestations of developmental hemostasis with respect to clinical disease phenotypes. It will discuss bleeding diagnosis in neonates, dealing especially with the devastating complications of intracerebral and pulmonary hemorrhage in preterm infants. Neonates, especially the sickest preterm ones, are also extremely susceptible to thrombotic complications; thus, thrombosis in neonates will be reviewed, with special focus on arterial ischemic perinatal stroke. Based on the concept of developmental hemostasis, the phenotypes of clinically relevant bleeding or thrombotic disorders among neonates may differ from those of older infants and children. Treatment options for these conditions will be suggested and reviewed.