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Stroke Prevention in Older Adults: Recent Advances.
Spence, JD, Azarpazhooh, MR, Larsson, SC, Bogiatzi, C, Hankey, GJ
Stroke. 2020;(12):3770-3777
Abstract
The risks of stroke and dementia increase steeply with age, and both are preventable. At present, the best way to preserve cognitive function is to prevent stroke. Therapeutic nihilism based on age is common and unwarranted. We address recent advances in stroke prevention that could contribute greatly to prevention of stroke and dementia at a time when the aging of the population threatens to markedly increase the incidence of both. Issues discussed: (1) old patients benefit even more from lipid-lowering therapy than do younger patients; (2) patients with stiff arteries are at risk from a target systolic blood pressure <120 mm Hg; (3) the interaction of the intestinal microbiome, age, and renal function has important dietary implications for older adults; (4) anticoagulation with direct-acting oral anticoagulants should be prescribed more to old patients with atrial fibrillation; (5) B vitamins to lower homocysteine prevent stroke; and (6) most old patients in whom intervention is warranted for carotid stenosis would benefit more from endarterectomy than from stenting. An 80-year-old person has much to lose from a stroke and should not have effective therapy withheld on account of age. Lipid-lowering therapy, a more plant-based diet, appropriate anticoagulation or antiplatelet therapy, appropriate blood pressure control, B vitamins to lower homocysteine, and judicious intervention for carotid stenosis could do much to reduce the growing burden of stroke and dementia.
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2.
Non-Vitamin K Antagonist Oral Anticoagulant for Atrial Fibrillation in Obese Patients.
Wang, SY, Giugliano, RP
The American journal of cardiology. 2020;:176-183
Abstract
Four non-vitamin K antagonist oral anticoagulants (NOACs) are approved for use to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation (AF). However, data are limited regarding the use of NOACs in the obese population. This manuscript summarizes current concepts regarding obesity in patients with AF and reviews in depth the data on the efficacy and safety of NOACs in obese patients with AF. The Pubmed database was searched for relevant articles. When evaluating obese patients with AF, weight loss is important to reduce disease burden. Recent analyses of the four NOAC versus warfarin trials (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48) stratified by body mass index (BMI) demonstrate preserved efficacy with NOACs versus warfarin in obese patients, with similar risk of major bleeding. Although the data are limited in class III obese patients (body mass index ≥40kg/m2), the efficacy and safety of apixaban or edoxaban appears to be similar to warfarin in patients with BMI 40-50kg/m2. In conclusion, these new data should be considered in updated guidelines, which currently provide limited, and sometimes conflicting recommendations regarding the use of NOACs in obese patients, particularly in severely obese patients.
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3.
The rebirth of the contact pathway: a new therapeutic target.
Srivastava, P, Gailani, D
Current opinion in hematology. 2020;(5):311-319
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Abstract
PURPOSE OF REVIEW Anticoagulation with vitamin-K antagonists or direct oral anticoagulants is associated with a significant risk of bleeding. There is a major effort underway to develop antithrombotic drugs that have a smaller impact on hemostasis. The plasma contact proteins factor XI (FXI) and factor XII (FXII) have drawn considerable interest because they contribute to thrombosis but have limited roles in hemostasis. Here, we discuss results of preclinical and clinical trials supporting the hypothesis that the contact system contributes to thromboembolic disease. RECENT FINDINGS Numerous compounds targeting FXI or FXII have shown antithrombotic properties in preclinical studies. In phase 2 studies, drugs-targeting FXI or its protease form FXIa compared favorably with standard care for venous thrombosis prophylaxis in patients undergoing knee replacement. While less work has been done with FXII inhibitors, they may be particularly useful for limiting thrombosis in situations where blood comes into contact with artificial surfaces of medical devices. SUMMARY Inhibitors of contact activation, and particularly of FXI, are showing promise for prevention of thromboembolic disease. Larger studies are required to establish their efficacy, and to establish that they are safer than current therapy from a bleeding standpoint.
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4.
Treatment of thrombotic antiphospholipid syndrome in adults and children.
Madison, JA, Duarte-García, A, Zuo, Y, Knight, JS
Current opinion in rheumatology. 2020;(3):215-227
Abstract
PURPOSE OF REVIEW Antiphospholipid syndrome (APS), more common than once believed, is an autoimmune disease best known for its high risk of incident and recurrent thrombotic events. The approach to treatment potentially differs from treatment of thrombosis in the general population, and this article endeavors to review the latest updates on this topic. RECENT FINDINGS The epidemiology of APS is being increasingly elucidated by large population-based studies, with APS perhaps affecting as many as 1 in 2000 individuals. Vitamin K antagonists, aspirin, and heparinoids continue to have obvious roles in the management of patients with APS. There has recently been intensive study of direct oral anticoagulants in APS, with the most recent randomized studies raising concerns about their inferiority to vitamin K antagonists, at least in some subgroups. Other approaches to treating APS beyond anticoagulants and antiaggregants are also receiving increased attention in mechanistic and preclinical studies with an eye toward future roles in patients with refractory and/or microvascular disease. Pediatric APS is identified as an area in desperate need of additional prospective research. SUMMARY Progress continues to be made in pursuit of improving the lives of individuals afflicted with APS. The most important future directions would seem to involve leveraging modern molecular technologies in order to improve subphenotyping of antiphospholipid antibody-positive individuals. This will help personalize risk profiles and ideally define the optimal approach to therapy based on future risk, rather than past morbid events.
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Challenges and Opportunities in the Pharmacological Treatment of Acute Venous Thromboembolism in Children.
George, C, Rahman, M, Monagle, P
Paediatric drugs. 2020;(4):385-397
Abstract
Venous thromboembolism (VTE) is an important but historically under-recognized problem in pediatrics, with an incidence concentrated in hospitalized children. A number of specific VTE diseases with discrete triggers have been described, but the most common pediatric trigger is the presence of central venous access devices. VTE diseases, though heterogenous in etiology, are linked by the common therapeutic strategies shared by their management. Historically, the most commonly used drug therapies have been unfractionated heparin, low-molecular-weight heparins, and vitamin K antagonists, based on extrapolation from adult data rather than any specific pediatric trials. Although these widely used drugs appear safe and effective in expert hands, the historical lack of pediatric data is problematic in view of the recognized significant differences between children and adults with regards to hemostatic physiology, VTE etiology, and drug pharmacokinetics. The increasing adult usage of novel VTE pharmacotherapies such as direct oral anticoagulants (DOACs) has led to considerable interest in exploring the pediatric applications of these newer drugs. This review summarizes the advantages and disadvantages of existing VTE pharmacotherapies and outlines emerging novel pediatric VTE therapies, particularly DOACs, within the context of the current pediatric trial landscape.
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Energy expenditure and caloric targets during continuous renal replacement therapy under regional citrate anticoagulation. A viewpoint.
Jonckheer, J, Spapen, H, Malbrain, MLNG, Oschima, T, De Waele, E
Clinical nutrition (Edinburgh, Scotland). 2020;(2):353-357
Abstract
BACKGROUND Indirect calorimetry (IC) is the gold standard for measuring energy expenditure in critically ill patients However, continuous renal replacement therapy (CRRT) is a formal contraindication for IC use. AIMS To discuss specific issues that hamper or preclude an IC-based assessment of energy expenditure and correct caloric prescription in CRRT-treated patients. METHODS Narrative review of current literature. RESULTS Several relevant pitfalls for validation of IC during CRRT were identified. First, IC measures CO2 production (VCO2) and O2 consumption to calculate resting energy expenditure (REE) with the Weir equation. VCO2 measurements are influenced by CRRT because CO2 is exchanged during the blood purification process. CO2 exchange also depends on type of pre- and/or postdilution fluid(s). CO2 dissolves in different forms with dynamic but unpredictable impact on VCO2. Second, the effect of immunologic activation and heat loss on REE caused by extracorporeal circulation during CRRT is poorly documented. Third, caloric prescription should be adapted to CRRT-induced in- and efflux of different nutrients. Finally, citrate, which is the preferred anticoagulant for CRRT, is a caloric source that may influence IC measurements and REE. CONCLUSION Better understanding of CRRT-related processes is needed to assess REE and provide individualized nutritional therapy in this condition.
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Treatment of Vascular Thrombosis in Antiphospholipid Syndrome: An Update.
Kalmanti, L, Lindhoff-Last, E
Hamostaseologie. 2020;(1):31-37
Abstract
The antiphospholipid syndrome (APS) is an acquired autoimmune disorder associated with arterial, venous, or microvascular thrombosis and/or pregnancy complications mainly in young age. The diagnosis is made by the persistent detection of anticardiolipin antibodies, β2-glycoprotein I antibodies (β2GPIA), and/or lupus anticoagulants (LAs) for at least 12 weeks. Patients should present with at least one clinical and one laboratory criterion. Patients presenting with all three types of antibodies and vascular events are high-risk patients and should receive vitamin K antagonists (VKAs) as long as the antibodies persist. In patients with prior arterial thrombosis, VKA with or without low-dose aspirin is the current treatment of choice. The international normalized ratio (INR) should be between 2 and 3 although in some cases keeping the target INR above 3 may be necessary. Patients with venous thrombosis and negative LA may alternatively be treated with direct oral anticoagulants although more data are needed. Minimizing vascular risk factors is always necessary in APS patients. Aspirin can be given as primary prevention in asymptomatic patients with positive antiphospholipid antibodies without thrombosis or pregnancy complications especially when additional vascular risk factors are present. Catastrophic APS occurs in less than 1% of APS patients and presents as a thrombotic storm. Early use of a combined triple therapy such as anticoagulation, plasma exchange, and steroids with either or not addition of immunoglobulins is important to reduce mortality.
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Thrombotic risk in children undergoing orthopedic surgery.
Odent, T, de Courtivron, B, Gruel, Y
Orthopaedics & traumatology, surgery & research : OTSR. 2020;(1S):S109-S114
Abstract
Children are physiologically protected against venous thromboembolism (VTE). Specific triggering events or contributing factors have been identified in the majority of reported cases, which differs from the adult pathology where 50% of the thromboses are considered "idiopathic". This is a rare disease in children with an estimated frequency of less than 1/1000. The risk is highest in neonates, then decreases and increases again around 13 years to reach the same level as adults at 16 years. The risk of VTE is clearly higher in certain situations: significant trauma, prolonged immobilization, central venous catheter, stay in intensive care unit, inherited thrombophilia, cancer, obesity, oral contraceptives, etc. Thromboprophylaxis should not be used systematically, even in adolescents. Proper hydration and early mobilization form the basis of mechanical thromboprophylaxis. A prescription is only given after careful analysis of the child's risk factors and the orthopedic context. Thrombotic risk assessment scores - which are based on expert opinion and large VTE registers but have not been evaluated in clinical studies - are currently the most reliable method to evaluate the thrombotic risk in children and to prescribe thromboprophylaxis. Low-molecular weight heparin are the most commonly used thromboprophylaxis agents in children, with good tolerance and efficacy.
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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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10.
Meta-analysis Comparing Direct Oral Anticoagulants Versus Vitamin K Antagonists After Transcatheter Aortic Valve Implantation.
Ueyama, H, Kuno, T, Ando, T, Briasoulis, A, Fox, J, Hayashida, K, Takagi, H
The American journal of cardiology. 2020;(7):1102-1107
Abstract
Atrial fibrillation (AF) is a common co-morbidity in patients undergoing transcatheter aortic valve implantation (TAVI), but whether direct oral anticoagulants (DOACs) confer similar safety and efficacy compared with vitamin K antagonist (VKA) remains unclear in this population. The aim of our study was to investigate the safety and efficacy of DOACs compared with VKA in patients undergoing TAVI with concomitant indication of oral anticoagulation. PUBMED and EMBASE were searched through October 2019 for studies comparing DOACs versus VKA in patients undergoing TAVI with indication of oral anticoagulation. The main efficacy outcomes were all-cause mortality and stroke whereas the main safety outcome was major and/or life-threatening bleeding. Our search identified 5 eligible studies including 2,569 patients. Majority of patients had atrial fibrillation as indication of anticoagulation. There were no significant differences in all-cause mortality, major and/or life-threatening bleeding, and stroke in patients treated with DOACs versus VKA (odds ratio [OR] 1.07, 95% confidence interval [CI] [0.73 to 1.57], p = 0.72, OR = 0.85, 95% CI [0.64 to 1.12], p = 0.24, OR 1.52, 95% CI [0.93 to 2.48], p = 0.09, respectively). In conclusion, in patients undergoing TAVI with concomitant indication for oral anticoagulation, all-cause mortality, major and/or life-threatening bleeding, and stroke were similar between DOACs and VKA. Further large scale randomized controlled trials are needed to search the optimal oral anticoagulation regimen in this population.