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1.
Non-vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with atrial fibrillation.
Undas, A, Drabik, L
Anatolian journal of cardiology. 2020;(1):10-18
Abstract
Non-vitamin K antagonist oral anticoagulants (NOACs), or direct oral anticoagulants have not been tested in randomized trials conducted in patients with atrial fibrillation (AF), who had malignant disease. However, their use in cancer patients increases and real-life evidence for their effectiveness and safety in this vulnerable subset of patients is growing. The challenges of the use of NOACs in cancer patients with AF and the current expert opinions on this subject have been summarized in this review article.
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2.
Deleterious cardiovascular effect of exosome in digitalis-treated decompensated congestive heart failure.
Fu, JL, Yu, Q, Li, MD, Hu, CM, Shi, G
Journal of biochemical and molecular toxicology. 2020;(5):e22462
Abstract
Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis.
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3.
A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019).
Pazan, F, Collins, R, Gil, VM, Hanon, O, Hardt, R, Hoffmeister, M, Monteiro, P, Quinn, TJ, Ropers, D, Sergi, G, et al
Drugs & aging. 2020;(7):539-548
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Abstract
INTRODUCTION Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019. METHODS A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA. RESULTS A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A. CONCLUSION OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.
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Emergency Department Management of Recent-Onset Atrial Fibrillation.
Weant, KA, Matuskowitz, AJ, Gregory, H, Caporossi, J, Hall, GA
Advanced emergency nursing journal. 2020;(3):176-185
Abstract
Atrial fibrillation (AF) is the most common tachyarrhythmia managed in the emergency department (ED). Visits to the ED for a presentation of AF have been increasing in recent years, with an admission rate that exceeds 60% in the United States and contributes substantially to health care costs. Recent-onset AF-defined as symptom onset less than 48 hr-is a common ED presentation for which rate control or acute electrical or pharmacological cardioversion may be appropriate treatment modalities depending on patient-specific circumstances. The focus of this review is to discuss the current recommendations regarding the management of recent-onset nonvalvular AF in the ED, discuss medication administration considerations, and identify implementation strategies in the ED to optimize throughput and reduce hospital admissions.
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Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction in Patients With Nonalcoholic Fatty Liver Disease.
Packer, M
The American journal of medicine. 2020;(2):170-177
Abstract
The most common causes of chronic liver disease in the developed world-nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)-are the hepatic manifestations of an insulin-resistant state that is linked to visceral adiposity and systemic inflammation. NAFLD and NASH lead to an expansion of epicardial adipose tissue and the release of proinflammatory adipocytokines that cause microcirculatory dysfunction and fibrosis of the adjoining myocardium, resulting in atrial fibrillation as well as heart failure with a preserved ejection fraction (HFpEF). Inflammatory changes in the left atrium lead to electroanatomical remodeling; thus, NAFLD and NASH markedly increase the risk of atrial fibrillation. Simultaneously, patients with NAFLD or NASH commonly show diastolic dysfunction or latent HFpEF. Interventions include 1) weight loss by caloric restriction, bariatric surgery, or intensive exercise, and 2) drugs that ameliorate fat-mediated inflammation in both the liver and heart (eg, statins, metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and pioglitazone). Patients with NAFLD or NASH commonly have an inflammation-related atrial and ventricular myopathy, which may contribute to symptoms and long-term outcomes.
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6.
The Efficacy of Non-Vitamin K Antagonist Oral Anticoagulants in the Prevention of Left Atrial Thrombus in Patients With Atrial Fibrillation Compared With Vitamin K Antagonists: A Meta-Analysis.
Liu, J, Wu, Y, Li, S, Song, L, Hu, C
The heart surgery forum. 2020;(6):E733-E739
Abstract
BACKGROUND There is still a paucity of data on the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) in the prevention of left atrial thrombus (LAT) formation before cardioversion or catheter ablation. To assess the efficacy of NOACs in the prevention of LAT in patients with non-valvular atrial fibrillation (NVAF) compared with vitamin K antagonists (VKAs), we conducted a meta-analysis. METHODS We searched PubMed, Embase, and the Cochrane Library databases. For meta-analysis, dichotomous variables were analyzed by using the odds ratios (OR) computed using the Mantel Haenszel method (random models). All results were reported with 95% confidence intervals (CI). RESULTS A total of 13 studies (one randomized controlled investigation and 12 observational studies) were included in the meta-analysis. There was no statistically significant difference between the NOACs and VKAs groups with respect to the odds of LAT/LAAT formations (OR 0.79; 95% CI: 0.52-1.21; P = .29; (I2 = 14%). CONCLUSIONS NOACs were as effective as VKAs in the prevention of LAT/LAAT formation in patients with NVAF. Though patients on NOACs therapy showed a lower incidence of LAT/LAAT formation compared with VKAs, it was not significant (P = .29).
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7.
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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Effect of non-vitamin-K oral anticoagulants on stroke severity compared to warfarin: a meta-analysis of randomized controlled trials.
Costello, M, Murphy, R, Judge, C, Ruttledge, S, Gorey, S, Loughlin, E, Hughes, D, Nolan, A, O'Donnell, MJ, Canavan, M
European journal of neurology. 2020;(3):413-418
Abstract
BACKGROUND AND PURPOSE In addition to lowering stroke risk, warfarin use is also associated with reduced stroke severity in patients with atrial fibrillation and acute ischaemic stroke. It was sought to determine whether the effect of non-vitamin-K oral anticoagulants (NOACs), compared to warfarin, differed by stroke severity. METHODS Phase III randomized controlled trials with participants who were randomized to receive NOACs or warfarin for stroke prevention in the setting of non-valvular atrial fibrillation were identified. Stroke was classified into two categories, fatal or disabling stroke and non-disabling stroke, and meta-analyses were completed for both outcomes and for comparative case fatality of stroke amongst trials. RESULTS Five randomized controlled trials met our inclusion criteria. In clinical trials evaluating the NOACs usually prescribed in clinical practice (four trials), acute stroke was reported in 1403 (1.86%) participants, 787 (1.04%) in the NOAC group [386 (0.51%) fatal or disabling, 401 (0.53%) non-disabling] and 616 (0.82%) in the warfarin group [367 (0.49%) fatal or disabling, 249 (0.33%) non-disabling]. On meta-analysis NOACs were significantly superior to warfarin for fatal or disabling stroke (odds ratio [OR] 0.77; 95% confidence interval [CI] 0.66-0.89, I2 = 21%) and non-disabling stroke (OR 0.85; 95% CI 0.73-0.98, I2 = 2%). The case fatality of stroke was no different between groups (OR 0.90, 95% CI 0.75-1.13, I2 = 0%), but the point estimate favoured NOACs. CONCLUSION In phase III trials of NOACs, for prevention of stroke in atrial fibrillation, NOACs are associated with a lower risk of both fatal/disabling and non-disabling stroke compared to warfarin.
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Clinical Performance of Nonvitamin K Antagonist Oral Anticoagulants in Real-World Obese Patients with Atrial Fibrillation.
Russo, V, Bottino, R, Rago, A, Papa, AA, Liccardo, B, D'Onofrio, A, Golino, P, Nigro, G
Seminars in thrombosis and hemostasis. 2020;(8):970-976
Abstract
The prevalence of both atrial fibrillation (AF) and obesity has steadily increased. Nonvitamin K antagonist oral anticoagulants (NOACs) have been shown to be more effective and safer than vitamin K antagonists (VKAs) for long-term stroke prevention in patients with nonvalvular AF. There are still limited data in the literature regarding performance of NOACs in obese patients with AF in the "real world." The aim of our study was to compare the safety and effectiveness of NOACs versus well-controlled VKA therapy in obese AF patients in a "real-world" setting. Here, we have considered patients with AF and obesity (body mass index [BMI] > 30 kg/m2) on NOAC or VKA therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MBs) and thromboembolic events (composite of ischemic stroke, transient ischemic attack, and systemic embolism) was respectively considered primary safety and effectiveness outcomes. We identified 1,047 AF patients with obesity who received NOAC (n = 272) or VKA (n = 775) treatment. After propensity score matching analysis, 248 NOAC and 496 VKA recipients with similar clinical characteristics, including BMI (34.8 ± 3.4 in NOAC vs. 35.1 ± 3.8 in the VKA group; p = 0.50), were evaluated. The mean follow-up was 39 ± 7 months. The incidence rate of thromboembolic events was 1.10 per 100 person-years (0.67 in NOAC vs. 1.28 in the VKA group; hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.22-1.22; p = 0.19). The incidence rate of MB was 1.9 per 100 person-years (1.1 in NOAC vs. 2.28 in the VKA group; HR: 0.46; 95% CI: 0.24-0.88; p = 0.04). The incidence rate of intracranial hemorrhage was 0.4 per 100 person-years (0.27 in NOAC vs. 0.47 in the VKA group; HR: 0.57; 95% CI: 0.12-2.73; p = 0.48). A positive net clinical benefit (NCB) of NOACs over VKAs was found (+0.91). Presence of anemia (HR: 1.75; p = 0.003) and concomitant use of antiplatelet drugs (HR: 2.41; p = 0.001) were found to be independent predictors of MB; moreover, age (HR: 1.65; p = 0.003) was an independent predictor of thromboembolic events. Our data support the hypothesis of safe and effective use of NOACs in patients with AF and obesity, justified by a statistically significant lower incidence of MB and a favorable NCB over VKAs.
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10.
Bisphosphonates and atrial fibrillation: revisiting the controversy.
Fazmin, IT, Huang, CL, Jeevaratnam, K
Annals of the New York Academy of Sciences. 2020;(1):15-26
Abstract
Bisphosphonates (BPs) are widely prescribed drugs used to treat osteoporosis, commonly arising in postmenopausal women and in chronic glucocorticoid use. Their mechanism of action is through inhibiting osteoclast-induced bone remodeling, and they also possess calcium sequestering properties. Common side effects involve the gastrointestinal system and rare but serious side effects, including osteonecrosis of the jaw. However, a link between BPs and atrial fibrillation (AF) has been proposed, with early clinical trials, such as the Fracture Intervention Trial and the HORIZON Pivotal Fracture Trial, reporting that BPs are associated with increased risk of AF. Nevertheless, subsequent studies have reported contrasting results, ranging from no effect of BPs to antiarrhythmic effects of BPs. Preclinical and electrophysiological studies on any proarrhythmic effect of BPs are limited in scope and number, but suggest possible mechanisms that include antiangionesis-related myocardial remodeling, calcium handling abnormalities, and inflammatory changes. Contrastingly, some studies indicate that BPs are antiarrhythmic by inhibiting fibrotic myocardial remodeling. In order to continue established clinical prescribing of BPs within absolute margins of safety, it will be necessary to systematically rule in/rule out these mechanisms. Thus, we discuss these studies and examine in detail the potential mechanistic links, with the aim of suggesting further avenues for research.