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1.
Use of Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombi: A Systematic Review.
Sedhom, R, Abdelmaseeh, P, Megaly, M, Asinger, R
The American journal of medicine. 2020;(11):1266-1273.e6
Abstract
The off-label use of direct oral anticoagulants (DOACs) for the treatment of left ventricular thrombi has grown over the past several years given the ease of administration, absence of a requirement for international normalized ratio (INR) monitoring, and freedom from dietary restrictions; however, the evidence for their safety and efficacy is contradictory. We systematically searched PubMed and Google Scholar from January 1, 2009, to April 25, 2020, for studies of DOACs for treatment of left ventricular thrombi. Fifty-three articles (of 1,168 patients) met our inclusion criteria. We found that the studies have reached conflicting results; based on our findings, their routine use for the treatment of left ventricular thrombi cannot be recommended. Adequately powered randomized controlled trials are needed to determine the safest and most effective treatment for left ventricular thrombi.
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2.
Clot Analog Attenuation in Non-contrast CT Predicts Histology: an Experimental Study Using Machine Learning.
Velasco Gonzalez, A, Buerke, B, Görlich, D, Fobker, M, Rusche, T, Sauerland, C, Meier, N, Jeibmann, A, McCarthy, R, Kugel, H, et al
Translational stroke research. 2020;(5):940-949
Abstract
Exact histological clot composition remains unknown. The purpose of this study was to identify the best imaging variables to be extrapolated on clot composition and clarify variability in the imaging of thrombi by non-contrast CT. Using a CT-phantom and covering a wide range of histologies, we analyzed 80 clot analogs with respect to X-ray attenuation at 24 and 48 h after production. The mean, maximum, and minimum HU values for the axial and coronal reconstructions were recorded. Each thrombus underwent a corresponding histological analysis, together with a laboratory analysis of water and iron contents. Decision trees, a type of supervised machine learning, were used to select the primary variable altering attenuation and the best parameter for predicting histology. The decision trees selected red blood cells (RBCs) for correlation with all attenuation parameters (p < 0.001). Conversely, maximum attenuation on axial CT offered the greatest accuracy for discriminating up to four groups of clot histology (p < 0.001). Similar RBC-rich thrombi displayed variable imaging associated with different iron (p = 0.023) and white blood cell contents (p = 0.019). Water content varied among the different histologies but did not in itself account for the differences in attenuation. Independent factors determining clot attenuation were the RBCs (β = 0.33, CI = 0.219-0.441, p < 0.001) followed by the iron content (β = 0.005, CI = 0.0002-0.009, p = 0.042). Our findings suggest that it is possible to extract more and valuable information from NCCT that can be extrapolated to provide insights into clot histological and chemical composition.
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3.
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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4.
Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve.
Jawitz, OK, Wang, TY, Lopes, RD, Chavez, A, Boyer, B, Kim, H, Anstrom, KJ, Becker, RC, Blackstone, E, Ruel, M, et al
American heart journal. 2020;:91-99
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Abstract
Vitamin K antagonists are the only approved oral anticoagulants for long-term prophylaxis against valve thrombosis and thromboembolism in patients with a mechanical heart valve. Despite the proven efficacy and safety of anticoagulation with the oral direct factor Xa inhibitor apixaban compared with warfarin in high-risk populations including subjects with atrial fibrillation or with venous thromboembolism, it remains unknown whether patients with a mechanical heart valve can be safely managed with apixaban. The On-X Aortic Heart Valve and On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft may have lower rates of valve thrombosis and thromboembolism than conventional bileaflet and tilting disc valves due its unique pyrolytic carbon composition and flared inlet design. DESIGN PROACT Xa is a randomized, multicenter, open-label, active-controlled trial comparing apixaban with warfarin in patients with an On-X Aortic Heart Valve or On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft. The study will randomize approximately 1,000 patients from approximately 60 sites in North America who underwent aortic valve replacement at least 3 months prior. Patients will be randomized 1:1 to receiving apixaban 5 mg twice daily or warfarin with a target international normalized ratio of 2.0-3.0. The last randomized participant will be followed for at least 2 years. The primary efficacy outcome is the composite of valve thrombosis and valve-related thromboembolism, and the primary safety outcome is major bleeding. Assuming the primary outcome occurs in warfarin-anticoagulated patients at a rate of 1.75%/patient-year, the study has more than 90% power to assess noninferiority of apixaban treatment with an absolute noninferiority margin of 1.75%/patient-year. A second co-primary analysis is to compare the hazard rate for the apixaban arm to twice the objective performance criterion for thromboembolism and valve thrombosis, that is, 3.4%/patient-year. SUMMARY PROACT Xa will determine whether patients with an On-X Aortic Heart Valve can be anticoagulated with apixaban as an alternative to warfarin.
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Safety and Efficacy of Double Antithrombotic Therapy With Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.
Capodanno, D, Di Maio, M, Greco, A, Bhatt, DL, Gibson, CM, Goette, A, Lopes, RD, Mehran, R, Vranckx, P, Angiolillo, DJ
Journal of the American Heart Association. 2020;(16):e017212
Abstract
Background The optimal antithrombotic therapy for patients with atrial fibrillation undergoing percutaneous coronary intervention is a topic of debate. We aimed at defining the efficacy and safety of double antithrombotic therapy with single antiplatelet therapy (SAPT) plus a non-vitamin K antagonist oral anticoagulant (NOAC) against triple antithrombotic therapy with dual antiplatelet therapy (DAPT) added to a vitamin K antagonist (VKA), illustrating the pooled cumulative distribution of events, the ranking of different NOACs tested in NOAC+SAPT combination strategies, and the state of the current evidence in the field. Methods and Results Randomized controlled trials meeting the inclusion criteria were identified. The primary efficacy end point was the composite of trial-defined major adverse cardiac events. The primary safety end point was clinically significant bleeding. Secondary end points were the components of primary end points. Trial-level pairwise and Bayesian network meta-analyses, reconstructed Kaplan-Meier analyses, and trial sequential analysis were performed. Four randomized controlled trials (10 969 patients) were included. No differences were found in terms of major adverse cardiac events (hazard ratio [HR], 1.07; 95% CI, 0.94-1.22), and the NOAC+SAPT strategy showed a lower rate of clinically significant bleeding compared with VKA + DAPT (HR, 0.56; 95% CI, 0.39-0.80). These results were consistent in reconstructed Kaplan-Meier analyses. In the Bayesian network meta-analysis, different NOACs displayed diverse risk-benefit profiles. Trial sequential analyses suggest that the evidence for the similarity in major adverse cardiac events compared with VKA + DAPT and the bleeding risk reduction observed with NOAC+SAPT is likely to be conclusive. Conclusions NOAC+SAPT does not increase the risk of major adverse cardiac events and reduces the risk of bleeding compared with VKA + DAPT in AF patients undergoing percutaneous coronary intervention. Various NOACs may have different risk-benefit profiles in combination strategies. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42020151089.
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New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update.
Genovese, G, Di Zenzo, G, Cozzani, E, Berti, E, Cugno, M, Marzano, AV
Frontiers in immunology. 2019;:1506
Abstract
There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.
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Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation.
Roullet, S, Labrouche, S, Mouton, C, Quinart, A, Nouette-Gaulain, K, Laurent, C, Freyburger, G
Journal of clinical pathology. 2019;(1):58-65
Abstract
AIMS: Diagnosis of hyperfibrinolysis in orthotopic liver transplantation (OLT) remains challenging. Euglobulin clot lysis time (ECLT) is not adapted to clinical situations. ROTEM is specific but seldom sensitive to hyperfibrinolysis. The Lysis Timer assesses 'Global Fibrinolytic Capacity' in citrated plasma (GFC/LT). GFC/LT associates reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA)), turbidity signal acquisition by the Lysis Timer, and dedicated software converting the digital signal into an optical curve. A visual check of the curves was systematic to ascertain the lysis time values calculated by the software. The primary aim of this prospective observational study was to evaluate the ability of GFC/LT to recognise hyperfibrinolysis during OLT. The secondary aim was to compare its results with ROTEM maximum lysis (EXTEM ML) and with standard laboratory tests. METHODS Thirty consecutive adult patients undergoing OLT were included (NCT03012633). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis parameters were assayed at five sample times. RESULTS GFC/LT was correlated with ECLT, plasmin activator inhibitor 1 antigen and activity and t-PA activity (r=0.490, 0.681, 0.643 and -0.359, respectively). Hyperfibrinolysis was defined as ECLT ≤60 min. Receiver operating characteristic curve analysis showed that GFC/LT with a threshold of 31 min detected hyperfibrinolysis with a sensitivity of 0.88 (95% CI 0.73 to 0.96), a specificity of 0.68 (95% CI 0.56 to 0.78) and an area under the curve (AUC) of 0.85 (95% CI 0.74 to 0.94). EXTEM ML >12% did not detect hyperfibrinolysis (sensitivity 0.38 (95% CI 0.24 to 0.55), specificity 0.95 (95% CI 0.86 to 0.99) and AUC 0.60 (95% CI 0.46 to 0.75)). CONCLUSIONS GFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with the other tests of fibrinolysis. TRIAL REGISTRATION NUMBER NCT03012633.
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Dual versus triple antithrombotic therapy: is there a role for direct oral anticoagulants in arterial thrombosis?
Garcia-Ropero, A, Santos-Gallego, CG, Zafar, MU, Badimon, JJ
Drugs of today (Barcelona, Spain : 1998). 2019;(3):197-214
Abstract
The number of patients receiving dual antiplatelet therapy with an additional indication for long-term oral anticoagulation has substantially increased over time. This population is facing an unacceptable risk of bleeding events, particularly among elderly individuals, who are especially vulnerable to complications. Further strategies to minimize this bleeding risk, including various drug combinations, different dosage regimens and even numerous attempts to find the appropriate duration of the treatment, have been evaluated in a multitude of randomized control trials. Moreover, the recent incorporation of the direct oral anticoagulants (DOACs) to the therapeutic armamentarium may represent an alternative to treat such patients, since they have demonstrated to be noninferior to the classic vitamin K antagonists and with lower bleeding rates. The aim of this review is to summarize the most recent literature on the use of DOACs in patients with an indication for dual antiplatelet therapy (mostly subjects with coronary artery disease) and also an established indication for chronic anticoagulation (chiefly individuals with nonvalvular atrial fibrillation). The role of DOACs in ischemic heart disease alone is also discussed.
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Recurrent Thrombosis With Direct Oral Anticoagulants in Antiphospholipid Syndrome: A Systematic Literature Review and Meta-analysis.
Sanchez-Redondo, J, Espinosa, G, Varillas Delgado, D, Cervera, R
Clinical therapeutics. 2019;(9):1839-1862
Abstract
PURPOSE The treatment of thrombosis in patients with antiphospholipid syndrome (APS) usually requires long-term anticoagulation with vitamin K antagonists. The effectiveness of direct oral anticoagulants (DOACs) in APS has not been fully addressed. The purpose of this research was to analyze the efficacy (thrombotic event-free time) and tolerability (bleeding events) of DOACs in patients with APS. METHODS We performed a descriptive analysis of a systematic review of data from patients with APS treated with DOACs reported in the literature, via EMBASE, PubMed, and the European League Against Rheumatism and American College of Rheumatology congresses. After systematic review, a meta-analysis of data from clinical trials was performed. FINDINGS A total of 728 patients, accounting for 731 courses of treatment with DOACs, were identified. The majority (48.3%) presented with triple anti-phospholipid antibody positivity. The prevalence of thrombosis during DOAC treatment was 13.9%. Analysis of risk factors for recurrent thrombosis suggested that a higher mean (SD) number of prior thrombotic events (1.80 [0.87] vs 1.67 [1.45]; P = 0.012), history of combined arterial and venous thrombosis (27.3% vs 9.2% [P < 0.0001]; odds ratio [OR] = 3.72 [95% CI, 1.91-7.25]), previous treatment with LMWH (9.8% vs 1.1% [P = 0.04]; OR = 9.95 [95% CI, 1.08-91.97]), use of immunosuppressant treatment (41.7% vs 12.7% [P = 0.03]; OR = 4.9 [95% CI, 1.21-19.76]), and no reason to switch anticoagulant treatment other than patient's decision (32% vs 2.8% [P = 0.001]; OR = 16.24 [95% CI, 3.16-83.52]) were associated with a high risk for re-thrombosis. Meta-Analysis did not show statistically relevant difference in risk of thrombosis or bleeding comparing warfarin with DOACs. IMPLICATIONS The findings from this systematic literature review and meta-analysis suggest that patients treated with DOACs and having risk factors such as history of recurrent thrombosis, a history of combined arterial and venous thrombosis, or a need for immunosuppressant treatment, may have higer ratio of thrombotic recurrence. There are limited data to inform decisions on the use of DOACs in patients with APS with different or no risk factors.
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[Antithrombotic therapy and digestive endoscopy: a difficult management.].
De Francesco, V, Manta, R, Zullo, A
Recenti progressi in medicina. 2019;(11):535-542
Abstract
Antithrombotic therapy (antiplatelet and anticoagulant) is frequently used in clinical practice for the prevention of thromboembolic events in patients at risk, such as those with atrial fibrillation or pro-thrombotic conditions. On the other hand, endoscopic investigations on the upper digestive tract (gastroscopy, endoscopic retrograde colangiopancreatography) and lower (colonoscopy) are increasingly performed to prevent, diagnose and treat different diseases of digestive tract. Therefore, it is not uncommon for a patient to undergo endoscopic examination while taking antithrombotic therapy. The pharmacological management of these patients requires a careful balance between the haemorrhagic risk linked to the continuation of therapy and the hemorrhagic risk inherent to the endoscopic procedure, particularly when an operative procedure (polypectomy, sphincterotomy, etc.) is required. Beyond classical anticoagulants (vitamin K antagonists, dicumarolici), the so-called "direct-acting anticoagulants" have been recently introduced, and management of these drugs in before an endoscopic examination is different. Since endoscopic procedures are largely scheduled as "open access" directly by general practitioner, she/he is clearly involved in the management of these patients. This review aims to report the recommendations of international guidelines on this field, and to provide some schematic tools for performing a correct management of patients on antithrombotic therapy before gastrointestinal endoscopy.