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A literature search was carried out by screening MEDLINE for the terms dabigatran, rivaroxaban, apixaban, P-glycoprotein, and atrial fibrillation from 1998 to 2013. Randomized clinical trials, longitudinal studies, case series, and case reports were included.
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Major and moderate pDDIs with warfarin are very common in inpatients and are associated with INR results outside the therapeutic range. Pharmaceutical interventions concerning the management of interactions by providing information to physicians can improve the patient safety.
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In patients with nonvalvular atrial fibrillation, >90 % of thrombi are detected in the left atrial appendage (LAA). In particular these observations have resulted in the development of catheter-based LAA closure as an approach for stroke prevention in patients with nonvalvular atrial fibrillation in recent years. A preliminary randomized trial provided promising data with respect to efficacy and safety of this approach as compared to anticoagulation with warfarin. The safety of the procedure has been significantly improved in recent years due to procedural experience and refinement of implanted devices. In current clinical practice, this approach is particularly used for patients with nonvalvular atrial fibrillation, a significant ischemic risk (CHA2DS2-VASc score ≥2), and a high bleeding risk, i. e., in patients in whom there are relevant concerns with respect to long-term anticoagulation. The present article discusses the data from randomized clinical studies and registries, the present guideline recommendations, and the practical clinical use of LAA closure for stroke prevention.
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Nine RCTs with a total of 3538 patients were considered. None of the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical interventions. Overall, the risk of bias was low in most of the studies. LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.41 to 0.93) with no evidence of heterogeneity (I(2) = 0%). The number needed to treat to prevent a symptomatic VTE was 60. LMWH was associated with a 60% increase in major bleeding when compared with inactive control, although this was not statistically significant (RR 1.57, 95% CI 0.69 to 3.60; I(2) = 10%). There was a 45% reduction in overall VTE (RR 0.55, 95% CI 0.34 to 0.88; I(2) = 0%) while for symptomatic pulmonary embolism, asymptomatic VTE, minor bleeding and one-year mortality the differences between the LMWH and control groups were not statistically significant. The effect of the vitamin K antagonist warfarin on preventing symptomatic VTE, measured in only one study, was not statistically significant (RR 0.15, 95% CI 0.02 to 1.20). In one RCT of patients with myeloma, LMWH was associated with a 67% reduction in symptomatic VTE (RR 0.33, 95% CI 0.14 to 0.83) compared with warfarin, with no differences in major bleeding. Antithrombin, evaluated in one study on paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control.
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The high budgetary impact of moving to a scenario of widespread substitution of warfarin for Dabigatran supports the restriction of this therapeutic strategy to subgroups of patients at high risk or difficult control.
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In this study both settings achieved good therapeutic control of warfarin treatment with a minor advantage for PHCC over ACC, and better results for men, especially in the PHCC setting. As patient characteristics differ between the PHCC and ACC, it is important to conduct further randomized studies to discern the best practice locally for warfarin management also after the introduction of new drugs.
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Monitoring warfarin anticoagulation in patients with thrombotic antiphospholipid syndrome (APS) may be complicated by the sensitivity of different thromboplastins to lupus anticoagulant. The aim of this study was to compare the degree of anticoagulation intensity in thrombotic APS and non-APS patients (50 in each group) on long-term warfarin, by measurement of the INR with two widely available thromboplastins with instrument-specific ISI values, and to investigate the potential role of amidolytic FX levels and thrombin generation (TG) testing in the assessment of anticoagulant intensity in thrombotic APS patients. There were no overall differences in INR between reagents or patient groups, but 20% (10/50) of APS patients showed ≥0.5 INR unit difference between reagents, which would have resulted in altered clinical management in some patients. FX levels were useful in assessing anticoagulation intensity for INR 2.0-3.0, but showed poor utility at INR ≥3.5 where the lowest measured FX level was 12IU/dL. In contrast, ETP and peak thrombin showed significant inverse correlations with the INR, suggesting that TG testing may be helpful in the determination of true anticoagulant intensity in APS patients, including those with ≥3.5 INR. TG testing also highlighted a subgroup of APS patients with increased peak thrombin relative to the intensity of anticoagulation as assessed by INR and FX, suggesting that TG testing may be useful in identifying an ongoing prothrombotic state in patients with apparently adequate anticoagulation intensity as assessed by INR.
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Stroke associated with non-valvular atrial fibrillation (NVAF) is one of the most important subtypes of ischemic stroke, and its importance is becoming even more apparent in an aging population. To assess the risk of stroke associated with NVAF, the CHADS2 and CHA2DS2-VASc scores are mainly used. Such scores can be used to predict the recurrence and prognosis of ischemic stroke. In addition, new oral anticoagulants (NOACs) and devices are being evaluated in the prevention of stroke associated with NVAF in addition to treatment with the conventional oral anticoagulant, warfarin. Since clinical experience with NOACs is not globally sufficient, a cautious approach is needed.
The number of valid responses was 157 (28.5%). The number of pregnant women who were diagnosed as having APS was 118.7 patients/year in 53 of 157 hospitals (33.8%). With respect to aPL measurements, 128 out of 157 hospitals (81.5%) determined one or more anticardiolipin antibodies or β2GPI-dependent anticardiolipin antibodies with one or more lupus anticoagulants; however aPL tests of only 2 hospitals (1.3%) covered all aPLs defined in the classification criteria. The obstetricians were responsible for treatments in 33.1% to 42.3% of the hospitals. The treatment methods or duration of treatments did not reach to the general consensus.
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When assessed using the 2012 Canadian Cardiovascular Society AF guidelines, the proportion of patients receiving appropriate SPAF therapy in this primary care setting decreased substantially. All patients with CHADS2 scores of 0 or 1 should be reassessed to ensure that they are receiving optimal stroke prevention treatment.
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Percutaneous approaches to left atrial appendage (LAA) closure are being developed for stroke prophylaxis in atrial fibrillation patients as an alternative to warfarin. Non-randomized clinical trials suggested that the first of these devices, the percutaneous left atrial appendage transcatheter occlusion (PLAATO) device, is safe and reduces stroke risk. Percutaneous closure has the potential limitation of incomplete exclusion of LAA from the systemic circulation, which could potentially lead to thrombus formation and stroke. This study investigated the interaction between residual blood flow in the LAA after percutaneous closure with PLAATO and risk of stroke.
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A meta-analysis of double blind randomized controlled trials (RCTs) was performed.
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There are few recent European studies of mortality after intracerebral hemorrhage (ICH), particularly long-term follow-up studies. No previous European studies have included information on leukoaraiosis.
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The aim of the study was to develop quality indicators signalling the potential discontinuation of previously prescribed medications for chronic diseases when residents return to LTC following an acute-care hospitalization.
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Human serum albumin (HSA) is involved physiologically in heme scavenging; in turn, heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, the allosteric effect of ibuprofen and warfarin on the local atomic structure around the ferric heme-Fe (heme-Fe(III)) atom of HSA-heme-Fe (HSA-heme-Fe(III)) has been probed by Fe-K edge X-ray absorption spectroscopy (XAS). The quantitative analysis of the Fe-K edge extended X-ray absorption fine structure (EXAFS) signals and modeling of the near edge (XANES) spectral features demonstrated that warfarin and ibuprofen binding modify the local structure of the heme-Fe(III). Combined XAS data analysis and targeted molecular dynamics (MD) simulations provided atomic resolution insights of protein structural rearrangements required to accommodate the heme-Fe(III) upon ibuprofen and warfarin binding. In the absence of drugs, the heme-Fe(III) atom is penta-coordinated having distorted 4+1 configuration made by the nitrogen atoms of the porphyrin ring and the oxygen phenoxy atom of the Tyr161 residue. MD simulations show that ibuprofen and warfarin association to the secondary fatty acid (FA) binding site 2 (FA2) induces a reorientation of domain I of HSA-heme-Fe(III), this leads to the redirection of the His146 residue providing an additional bond to the heme-Fe(III) atom, providing the 5+1 configuration. The comparison of Fe-K edge XANES spectra calculated using MD structures with those obtained experimentally confirms the reliability of the proposed structural model. As a whole, combining XAS and MD simulations it has been possible to provide a reliable model of the heme-Fe(III) atom coordination state and to understand the complex allosteric transition occurring in HSA-heme-Fe(III) upon ibuprofen and warfarin binding.
The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (≥7 days but <1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P-adj =0.015) and permanent AF (1.95%/year; P-adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P-adj <0.001) and permanent AF (4.4%/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment.
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Acute myocardial infarction (MI) in young adults is rare. Clinicopathological conditions such as nephrotic syndrome, antiphospholipid syndrome, spontaneous coronary artery spasms or embolism can be attributed to such events. In this case report, we present a 30-year-old male who had his first MI at the age of 20 years. He received percutaneous intervention as initial treatment. Despite aggressive risk factor management, he continued to have acute coronary events and was later diagnosed with antiphospholipid syndrome (APS). At the same time, he was diagnosed with severe chronic thromboembolic pulmonary hypertension and severe tricuspid regurgitation. He underwent pulmonary endartererectomy, tricuspid annuloplasty and radial artery bypass graft to the first obtuse marginal artery. Warfarin therapy was initiated upon the diagnosis of APS. Despite being therapeutic on warfarin and aggressive risk factor management, he had yet another MI. Coronary angiogram at this time showed fresh occlusion of the right coronary artery at the mid-segment, and the patient received two overlapping stents that achieved a good effect. This case emphasizes the importance of awareness, early recognition and aggressive management of patients with APS presenting chest pain or acute coronary events. Despite appropriate treatment, such as risk factor management and percutaneous interventions, recurrence of an acute coronary event is high. The presentation of younger patients with recurrent coronary events but no significant risk factors of atherosclerosis should evoke the suspicion of APS-related coronary artery disease, and all risk factors should be aggressively managed.
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Patients with AF and ischaemic stroke were followed up 1 year and 5 years after stroke. Level of dependence (Barthel Index), disability (modified Rankin Scale), risk factors, mortality and stroke prophylaxis before and after stroke were analysed. All parameters were compared between men and women.
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The non-vitamin K antagonist oral anticoagulants (NOACs), such as the thrombin inhibitor (dabigatran) and the direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), have been shown to be at least as efficacious and safe as conventional oral anticoagulants, such as the vitamin K antagonists (VKAs) (e.g., warfarin), for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Each NOAC has various advantages and specific features, and therefore decisions regarding appropriate stroke prevention require individual assessment of stroke and bleeding risk on anticoagulation with VKA therapy and NOACs when starting on any of these drugs. This review briefly describes the results of the four NOACs clinical randomized trials and discusses how they might impact clinical practice and choice of anticoagulants in atrial fibrillation patients. Moreover, this review discusses the differences of the proposed management of antithrombotic therapy in several international guidelines and pragmatic issues of NOACs for stroke prophylaxis.
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Brucellosis is a zoonotic disease common in developing countries. Vascular complications, including arterial and venous, associated with Brucella infection have rarely been reported. A case of deep venous thrombosis (DVT) developing after a diagnosis of acute brucellosis in a young milkman is presented. A 26-year-old man presented with pain in the right leg. The patient's medical history included a diagnosis of brucellosis in our hospital where he had presented with complaints of weakness and fever. Peripheral venous Doppler ultrasound showed DVT, and the patient was treated with anticoagulants. The patient was discharged with warfarin therapy and anti-brucellosis treatment. Although rare, some infectious agents may cause vascular pathologies. Patients presenting with symptoms of DVT or similar vascular pathologies should be assessed for infectious agents, particularly in those coming from Brucella-endemic areas.
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A total of 148 residents new to warfarin therapy met all study inclusion criteria. Median age was 84 years; 69% were female. Median time to therapy discontinuation was 197 days (95% CI, 137-249) across all study residents. By 90 days after the initiation of therapy, 37% (95% CI, 28-47) of study residents had discontinued warfarin; by 1 year, 65% (54%-76%) had discontinued warfarin therapy. The multivariate Cox regression analysis found that the following factors were independently associated with discontinuation of warfarin therapy: age 65 to 74 years (hazard ratio [HR] = 3.01 [95% CI, 1.04-8.73]), female sex (HR = 0.45 [95% CI, 0.24-0.87]), Hispanic race/ethnicity (HR = 2.86 [95% CI, 1.30-6.26]), Midwest region (HR = 2.13 [95% CI, 1.02-4.48]), and Alzheimer disease or dementia (HR = 1.97 [95% CI, 1.05-3.68]).
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Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients.
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Nearly 60% of AF patients with high-quality TTR1 on warfarin maintained TTR ≥70% over the next 6 months. A minority deteriorated to very poor TTR. Patient features did not strongly predict TTR in the second 6-month period. Our analyses support watchful waiting for AF patients with initial high-quality warfarin anticoagulation before considering alternative anticoagulants.