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1.
Stroke prevention in atrial fibrillation: State of the art.
Li, YG, Lip, GYH
International journal of cardiology. 2019;:201-209
Abstract
Stroke prevention is the cornerstone of the management of patients with atrial fibrillation (AF). Individual stroke risk stratification is generally the first step of deciding whether oral anticoagulation (OAC) will benefit patients with AF. Given that existing approaches to the prediction of 'high-risk' subjects are of limited value, the initial focus should be the identification of 'low-risk' patients who do not need antithrombotic therapy. For this, the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 [2 points], diabetes mellitus, previous stroke/transient ischemic attack [2 points], vascular disease, age 65-74, female sex) performs well in identifying really low-risk patients (score of 0 in males or 1 in females), for whom OAC can be omitted. The approach to AF management has changed, with the non-vitamin K antagonist oral anticoagulants (NOACs) providing relatively better efficacy, safety and convenience compared with the traditional vitamin K antagonists (VKAs). The latter drugs are performing well, if attention is directed towards good quality anticoagulation control, as reflected by a time in therapeutic range (TTR) >70%. Nevertheless, OAC use remains suboptimal especially in some regions, such as Asia and Africa. Long-term adherence and quality of OAC use need to be maintained for better outcomes in patients with AF.
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2.
Heart Failure and Atrial Fibrillation, Like Fire and Fury.
Carlisle, MA, Fudim, M, DeVore, AD, Piccini, JP
JACC. Heart failure. 2019;(6):447-456
Abstract
Heart failure and atrial fibrillation are 2 common cardiovascular disorders that frequently complicate one another and exert a significant detrimental effect on cardiovascular health and well-being. Both heart failure and atrial fibrillation continue to increase in prevalence as the risk factors underlying each condition become more common. This review encompasses what is currently known about the epidemiology and pathophysiology of these comorbidities along with incorporation of landmark trials that have contributed to current guidelines. The focus is on clinically relevant considerations, including the contribution of inflammation in the pathophysiology of atrial fibrillation and heart failure. We explore the emerging role of catheter ablation relative to medical therapy in the management of heart failure with reduced ejection fraction, along with indications for biventricular pacing modalities in cardiac resynchronization therapy. We discuss current guideline-directed therapies and how practice models and national recommendations will likely change based on the most recent randomized controlled trials.
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3.
Anticoagulation in Venous Thromboembolism Prophylaxis in Medically Ill Patients: Potential Impact of NOACs.
Knotts, TL, Mousa, SA
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2019;(4):365-376
Abstract
While substantial evidence supports the use of standard-duration injectable anticoagulants for venous thromboembolism (VTE) prophylaxis, consensus is mixed about which agents may be preferred in acutely ill patients with ongoing need of VTE prophylaxis past the first 10-day duration of hospital stay and post-discharge. Non-vitamin K antagonist oral anticoagulants (NOACs) provide Factor Xa inhibition to prevent the thrombin generation essential in thromboembolism development, but evidence for the efficacy and safety of most NOACs is conflicting regarding extended-duration prophylaxis. Enoxaparin, a preferred injectable anticoagulant in standard-duration VTE prophylaxis, has shown an increased risk of major bleeding events when used in extended-duration prophylaxis, which outweighs its benefit. Rivaroxaban has demonstrated efficacy in extended-duration prophylaxis, but both rivaroxaban and apixaban have shown increased risks of major bleeding. Betrixaban remains the only NOAC approved in the USA for extended-duration VTE prophylaxis, and it demonstrates efficacy, with fewer adverse effects than other NOACs. This review evaluates the appropriateness of different NOAC agents compared with current therapies for the extended-duration VTE prophylaxis setting in medically ill populations.
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4.
United States Pharmacopeia Safety Review of Willow Bark.
Oketch-Rabah, HA, Marles, RJ, Jordan, SA, Low Dog, T
Planta medica. 2019;(16):1192-1202
Abstract
Willow bark (Salix spp.) is an ingredient in some dietary supplements. No serious adverse effects were reported from trials of willow bark extracts delivering 120 - 240 mg salicin (the purported active constituent) daily for up to 8 weeks. All studies involved adults only; none involved special subpopulations such as pregnant or breastfeeding women, or children. The most common adverse effects associated with willow bark are gastrointestinal; a few allergic reactions were also reported. Some publications advise caution when taking willow bark. There is a risk of increased bleeding in vulnerable individuals, salicylates cross the placenta and are eliminated slowly in newborns, some persons are sensitive or allergic to aspirin, and children are at risk of Reye syndrome. Concurrent use with other salicylate-containing medicines increases these risks. Metabolism of 240 mg salicin from willow bark could yield 113 mg of salicylic acid, yet dietary supplement products are not required to be labeled with warnings. In contrast, over-the-counter low-dose aspirin (81 mg strength), which delivers 62 mg salicylic acid, is required by law to include cautions, warnings, and contraindications related to its use in pregnant and nursing women, children, and other vulnerable subpopulations, e.g., those using anticoagulants. In the interest of protecting public health, the United States Pharmacopeia has included a cautionary labeling statement in the United States Pharmacopeia Salix Species monograph as follows: "Dosage forms prepared with this article should bear the following statement: 'Not for use in children, women who are pregnant or nursing, or by persons with known sensitivity to aspirin.'".
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5.
Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation.
Seiffge, DJ, Werring, DJ, Paciaroni, M, Dawson, J, Warach, S, Milling, TJ, Engelter, ST, Fischer, U, Norrving, B
The Lancet. Neurology. 2019;(1):117-126
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Abstract
BACKGROUND About 13-26% of all acute ischaemic strokes are related to non-valvular atrial fibrillation, the most common cardiac arrhythmia globally. Deciding when to initiate oral anticoagulation in patients with non-valvular atrial fibrillation is a longstanding, common, and unresolved clinical challenge. Although the risk of early recurrent ischaemic stroke is high in this population, early oral anticoagulation is suspected to increase the risk of potentially harmful intracranial haemorrhage, including haemorrhagic transformation of the infarct. This assumption, and current treatment guidelines, are based on historical, mostly observational data from patients with ischaemic stroke and atrial fibrillation treated with heparins, heparinoids, or vitamin K antagonists (VKAs) to prevent recurrent ischaemic stroke. Randomised controlled trials have subsequently shown that direct oral anticoagulants (DOACs; ie, apixaban, dabigatran, edoxaban, and rivaroxaban) are at least as effective as VKAs in primary and secondary prevention of atrial fibrillation-related ischaemic stroke, with around half the risk of intracranial haemorrhage. However, none of these DOAC trials included patients who had experienced ischaemic stroke recently (within the first few weeks). Clinicians therefore remain uncertain regarding when to commence DOAC administration after acute ischaemic stroke in patients with atrial fibrillation. RECENT DEVELOPMENTS Prospective observational studies and two small randomised trials have investigated the risks and benefits of early DOAC-administration initiation (most with a median delay of 3-5 days) in mild-to-moderate atrial fibrillation-associated ischaemic stroke. These studies reported that early DOAC treatment was associated with a low frequency of clinically symptomatic intracranial haemorrhage or surrogate haemorrhagic lesions on MRI scans, whereas later DOAC-administration initiation (ie, >7 days or >14 days after index stroke) was associated with an increased frequency of recurrent ischaemic stroke. WHERE NEXT?: Adequately powered randomised controlled trials comparing early to later oral anticoagulation with DOACs in ischaemic stroke associated with atrial fibrillation are justified to confirm the acceptable safety and efficacy of this strategy. Four such randomised controlled trials (collectively planned to include around 9000 participants) are underway, either using single cutoff timepoints for early versus late DOAC-administration initiation, or selecting DOAC-administration timing according to the severity and imaging features of the ischaemic stroke. The results of these trials should help to establish the optimal timing to initiate DOAC administration after recent ischaemic stroke and whether the timing should differ according to stroke severity. Results of these trials are expected from 2021.
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6.
Quality Appraisal of Guidelines on Cancer-Associated Thrombosis Using AGREE II Instrument and Analysis of Current Status of New Oral Anticoagulants.
Zhang, J, Xu, J, Zhang, W, Jiang, M, Liu, J, Xu, L, Liu, G, Zhao, Z
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2019;:1076029619846562
Abstract
Cancer-associated thrombosis (CAT) studies have increased in recent years and the quality of guidelines to guide the clinical practice of CAT prevention and treatment becomes crucial. The therapy status of new oral anticoagulants (NOACs) has been established in some thrombotic diseases, but the evidence for CAT remains unconvincing. The aim of this research is to evaluate the quality of CAT guidelines and discuss the role of NOAC in CAT. A search of articles was performed using PubMed/Medline, Chinese National Knowledge Infrastructure, and other authoritative websites. Search terms included guideline or guidance, consensuses, cancer, and thrombosis. Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool was used to evaluate the qualities of the guidelines. A total of 19 guidelines were screened out and evaluated, of which 8 were recommended, 5 were recommended after revision, and 6 were not recommended. For prevention and treatment of CAT, low-molecular-weight heparin is the most recommended, followed by vitamin K antagonist, unfractionated heparin, fondaparinux, and aspirin. New oral anticoagulant is optional in some cases of CAT treatment. Based on AGREE II assessment tool, the quality of CAT guidelines is inconsistent. Attention should be drawn to the quality of CAT guidelines during clinical practice. The role of NOAC in the treatment of CAT is gradually established but requires more supporting evidence from future clinical trials.
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7.
Comparison of All-Cause Mortality Following VTE Treatment Between Propensity Score-Adjusted Observational Studies and Matched Randomized Controlled Trials: Meta-Epidemiologic Study.
Coscia, C, Jaureguizar, A, Quezada, CA, Muriel, A, Monreal, M, Villén, T, Barbero, E, Chiluiza, D, Yusen, RD, Jimenez, D
Chest. 2019;(4):689-698
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Abstract
BACKGROUND It is unknown whether propensity score-adjusted observational studies produce results comparable to those of randomized controlled trials (RCTs) that address similar VTE treatment issues. METHODS The PubMed and Web of Science databases were systematically searched for propensity score-adjusted observational studies, RCTs, and meta-analyses of RCTs that estimated all-cause mortality following VTE treatment. After identifying distinct clinical treatment issues evaluated in the eligible observational studies, a standardized algorithm was used to identify and match at least one RCT or RCT meta-analysis publication for paired study design analyses. Meta-analyses were used to summarize groups of studies. Treatment efficacy statistics (relative ORs) were compared between the paired observational and RCT studies, and the summary relative ORs for all study design pairs were also calculated. RESULTS The observational and RCT study pairs assessed seven clinical treatment issues. Overall, the observational study-RCT pairs did not exhibit significantly different mortality estimates (summary relative OR, 0.89; 95% CI, 0.32-1.46; I2 = 23%). However, two of the seven treatment issue study pairs (thrombolysis vs anticoagulation for pulmonary embolism; once- vs twice-daily enoxaparin for VTE) exhibited a significantly different treatment effect direction, and there was a substantial (nonsignificant) difference in the magnitude of the effect in another two of the study pairs (rivaroxaban vs vitamin K antagonists for VTE; home treatment vs hospitalization for DVT). CONCLUSIONS This systematic comparison across seven VTE treatment topics suggests that propensity score-adjusted observational studies and RCTs often exhibit similar all-cause mortality, although differences in the direction or the magnitude of estimated treatment effects may occasionally occur. TRIAL REGISTRY PROSPERO; CRD42018087819; URL: http://www.crd.york.ac.uk/PROSPERO.
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8.
Uninterrupted anticoagulation with non-vitamin K antagonist oral anticoagulants in atrial fibrillation catheter ablation: Lessons learned from randomized trials.
Cardoso, R, Willems, S, Gerstenfeld, EP, Verma, A, Schilling, R, Hohnloser, SH, Okumura, K, Nordaby, M, Brouwer, MA, Calkins, H
Clinical cardiology. 2019;(1):198-205
Abstract
Catheter ablation has been established as a rhythm control strategy in selected patients with atrial fibrillation (AF) who have failed or wish to avoid anti-arrhythmic drugs. Uninterrupted oral anticoagulation with vitamin K antagonists (VKAs) peri-ablation is associated with a lower risk of thromboembolic and bleeding complications as compared to interrupted oral anticoagulation and bridging heparin. However, a substantial portion of patients with AF are treated with non-vitamin K antagonist oral anticoagulants (NOACs). Herein, we perform an in-depth review and comparison of three recent randomized trials of uninterrupted oral anticoagulation with NOACs vs VKAs in patients undergoing AF catheter ablation. Furthermore, we report pooled results of these randomized trials. The pooled incidence of major bleeding was significantly lower with NOACs as compared to VKAs (2% vs 4.9%, respectively; odds ratio [OR] 0.40; 95% confidence intervals [CI] 0.16-0.99). Similarly, cardiac tamponade was also reduced in the NOAC group (0.4% vs 1.5%; OR 0.27; 95% CI 0.07-0.97). Thromboembolic complications were not significantly different between groups. Overall, these findings support the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement's class I recommendation for uninterrupted NOAC use in patients undergoing AF catheter ablation.
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Anticoagulation in Patients With Advanced Chronic Kidney Disease: Walking the Fine Line Between Benefit and Harm.
Jegatheswaran, J, Hundemer, GL, Massicotte-Azarniouch, D, Sood, MM
The Canadian journal of cardiology. 2019;(9):1241-1255
Abstract
Chronic kidney disease affects more than 3 million Canadians and is highly associated with cardiovascular diseases that require anticoagulation, such as atrial fibrillation and venous thromboembolism. Patients with chronic kidney disease are at a problematic crossroads; they are at high risk of thrombotic conditions requiring anticoagulation and bleeding complications due to anticoagulation. The limited high-quality clinical evidence to guide decision-making in this area further compounds the dilemma. In this review, we discuss the physiology and epidemiology of bleeding and thrombosis in patients with kidney disease. We specifically focus on patients with advanced kidney disease (estimated glomerular filtration rate ≤ 30 mL/min) or who are receiving dialysis and focus on the nephrologist perspective regarding these issues. We summarize the existing evidence for anticoagulation use in the prevention of stroke with atrial fibrillation and provide practical clinical recommendations for considering anticoagulation use in this population. Last, we examine specific scenarios such as the use of a glomerular filtration rate estimating equation and dosing, the use of existing prediction tools for stroke and hemorrhage risk, current patterns of anticoagulation use (including during the dialysis procedure), and vascular calcification with vitamin K antagonist use in patients with chronic kidney disease.
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10.
Anticoagulation in Concomitant Chronic Kidney Disease and Atrial Fibrillation: JACC Review Topic of the Week.
Kumar, S, Lim, E, Covic, A, Verhamme, P, Gale, CP, Camm, AJ, Goldsmith, D
Journal of the American College of Cardiology. 2019;(17):2204-2215
Abstract
Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist as they share multiple risk factors, including hypertension, diabetes mellitus, and coronary artery disease. Although there is irrefutable evidence supporting anticoagulation in AF in the general population, these data may not be transferable to the setting of advanced CKD, where the decision to commence anticoagulation poses a conundrum. In this cohort, there is a progressively increased risk of both ischemic stroke and hemorrhage as renal function declines, complicating the decision to initiate anticoagulation. No definitive clinical guidelines derived from randomized controlled trials exist to aid clinical decision-making, and the findings from observational studies are conflicting. In this review, the authors outline the pathophysiological mechanisms at play and summarize the limited existing data related to anticoagulation in those with concomitant CKD and AF. Finally, the authors suggest how to approach the decision of whether and how to use oral anticoagulation in these patients.