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1.
MMW Fortschr Med ; 161(Suppl 6): 15-23, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31587168

RESUMO

BACKGROUND: Non-vitamin K-dependent oral anticoagulants (NOAC) have changed the management of patients with oral anticoagulation. This raises the question of which patients should preferably be anticoagulated with NOAC and which preferably with vitamin K antagonists (VKA). This discussion has so far been insufficiently conducted and often decided on a flat-rate basis in favor of the NOAC. METHOD: To clarify the question owhich form of anticoagulation - NOAC or VKA - is the best choice for patients with atrial fibrillation, an interdisciplinary team of experts met. RESULTS AND CONCLUSIONS: The experts discussed essential practical aspects of NOAC and VKA therapy. Based on typical clinical scenarios, they developed assistance, comments and tips on the differentiated use of oral anticoagulants in patients with atrial fibrillation. A criteria served amongst others practicability in daily medical practice, contraindications, side effects and interactions, but also the patient's desire. The advantages and disadvantages of therapy with VKA and NOAC were summarized in a table.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial , Vitamina K/antagonistas & inibidores , Administração Oral , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrinolíticos , Humanos , Modalidades de Fisioterapia
2.
Pan Afr Med J ; 33: 160, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31565122

RESUMO

Intra-alveolar bleeding is a rare and severe medical emergency due to numerous causes. We report the clinical case of a patient who could contribute to extend the literature on this subject. The study included a 62-year old man, with a history of a trial fibrillation, under anti-vitamins K antagonist admitted with dyspnoea of sudden onset associated with haemoptysis and practising self-medication using non-steroidal anti-inflammatory drugs. X-rays and chest scan showed diffuse bilateral alveolar opacities. Haemostatic screening tests on admission showed non-coagulable INR. The diagnosis of intra-alveolar bleeding was clinically and radiologically suspected and then confirmed by bronchial endoscopy with broncho-alveolar lavage (BAL) which detected uniformly hemorrhagic liquid. Previous studies of similar complications occurring after anti-vitamins K antagonists assumption are rare. In conclusion, it seems very important to emphasize the interest of strict and optimal clinico-biological monitoring of patients treated in anti-vitamins K antagonists to avoid an overdose which could contribute to a life-threatening severe haemorrhagic event.


Assuntos
Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Alvéolos Pulmonares/patologia , Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Dispneia/induzido quimicamente , Hemoptise/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina K/antagonistas & inibidores
3.
Lancet ; 394(10206): 1335-1343, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31492505

RESUMO

BACKGROUND: We aimed to assess the safety of edoxaban in combination with P2Y12 inhibition in patients with atrial fibrillation who had percutaneous coronary intervention (PCI). METHODS: ENTRUST-AF PCI was a randomised, multicentre, open-label, non-inferiority phase 3b trial with masked outcome evaluation, done at 186 sites in 18 countries. Patients had atrial fibrillation requiring oral anticoagulation, were aged at least 18 years, and had a successful PCI for stable coronary artery disease or acute coronary syndrome. Participants were randomly assigned (1:1) from 4 h to 5 days after PCI using concealed, stratified, and blocked web-based central randomisation to either edoxaban (60 mg once daily) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist (VKA) in combination with a P2Y12 inhibitor and aspirin (100 mg once daily, for 1-12 months). The edoxaban dose was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, bodyweight ≤60 kg, or concomitant use of specified potent P-glycoprotein inhibitors) were present. The primary endpoint was a composite of major or clinically relevant non-major (CRNM) bleeding within 12 months. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of their assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02866175, is closed to new participants, and follow-up is completed. FINDINGS: From Feb 24, 2017, through May 7, 2018, 1506 patients were enrolled and randomly assigned to the edoxaban regimen (n=751) or VKA regimen (n=755). Median time from PCI to randomisation was 45·1 h (IQR 22·2-76·2). Major or CRNM bleeding events occurred in 128 (17%) of 751 patients (annualised event rate 20·7%) with the edoxaban regimen and 152 (20%) of 755 patients (annualised event rate 25·6%) patients with the VKA regimen; hazard ratio 0·83 (95% CI 0·65-1·05; p=0·0010 for non-inferiority, margin hazard ratio 1·20; p=0·1154 for superiority). INTERPRETATION: In patients with atrial fibrillation who had PCI, the edoxaban-based regimen was non-inferior for bleeding compared with the VKA-based regimen, without significant differences in ischaemic events. FUNDING: Daiichi Sankyo.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico , Intervenção Coronária Percutânea , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/cirurgia , Idoso , Fibrilação Atrial/complicações , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Stents , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
4.
Eur J Vasc Endovasc Surg ; 57(5): 685-701, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31097186

RESUMO

OBJECTIVE/BACKGROUND: The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer. METHODS: A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method. RESULTS: Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high. CONCLUSION: Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.


Assuntos
Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/prevenção & controle , Fondaparinux/efeitos adversos , Fondaparinux/uso terapêutico , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Oligossacarídeos/efeitos adversos , Oligossacarídeos/uso terapêutico , Embolia Pulmonar/prevenção & controle , Prevenção Secundária , Trombose Venosa/prevenção & controle , Vitamina K/antagonistas & inibidores
5.
Int J Lab Hematol ; 41 Suppl 1: 40-48, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31069986

RESUMO

Vitamin K antagonists (VKAs) cannot be administered without regular monitoring in order to assure their efficacy and safety. Indeed, if well managed, the VKAs appear to be no less efficacious or safe than the newer direct oral anticoagulants (DOACs). Although it is claimed that no regular monitoring of the DOACs is needed, their levels are increasingly being measured under a variety of circumstances, for example, prior to surgery, in suspected overdose, to confirm effective reversal, in patients with malabsorption and to assess patient compliance. Although no therapeutic range has been identified for the DOACs, it has been demonstrated for dabigatran and edoxaban that their antithrombotic effect increases gradually with increasing concentrations and that the risk of major bleeding also gradually increases. Furthermore, it has been determined that almost all dabigatran-related thrombotic events occur in patients with the lowest quartile concentration of the drug. This suggests that to assure an ideal effect of DOACs in all patients taking them, some form of regular monitoring and dose tailoring should be performed. For the vitamin K antagonists, the best outcome is obtained using formal algorithms and centralized management. Furthermore, data suggest that replacing the standard prothrombin time as a monitoring test may increase the stability of VKA anticoagulation with consequent reduction in thromboembolism without an increase in bleeding. Thus, it is likely that the outcome of all current oral anticoagulants can be improved in the coming years by improving monitoring and tailoring their effect.


Assuntos
Anticoagulantes/farmacocinética , Fibrilação Atrial , Monitoramento de Medicamentos/métodos , Hemorragia , Tromboembolia Venosa , Vitamina K/antagonistas & inibidores , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/sangue , Fibrilação Atrial/tratamento farmacológico , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Humanos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/tratamento farmacológico
6.
Expert Opin Drug Metab Toxicol ; 15(6): 449-458, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31120800

RESUMO

Introduction: The inclusion of pharmacogenetics alongside clinical information in anticoagulant therapy offers the opportunity for a tailored approach to treatment according to individual patient characteristics. Areas covered: Literature was searched using PubMed database, focusing on pharmacogenetics of oral anticoagulants. Original research articles and review articles in English language were included in the literature reviewed. This article includes all information available for the genetic cause of inter-individual variability in anticoagulation response to oral anticoagulant drugs. The pharmacogenetics of VKAs and NOACs are described in detail. Expert opinion: There have been numerous studies focusing on the pharmacogenetics of VKAs, particularly warfarin. Current evidence suggests that known genetic and clinical factors explain a large proportion of the inter-individual variability in response to warfarin. Pharmacogenetic-based algorithms have been validated to determine their clinical utility with equivocal results. To date, only a limited number of mostly small studies on the pharmacogenetics of NOACs exists. The latter have highlighted genetic polymorphisms in specific genes that may affect clinical outcomes. Further evaluations of these polymorphisms are needed before firm conclusions can be drawn about the significance of pharmacogenetics on NOAC therapy.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Farmacogenética , Administração Oral , Algoritmos , Animais , Fibrilação Atrial/complicações , Humanos , Polimorfismo Genético , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem
7.
Int Heart J ; 60(3): 546-553, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31105152

RESUMO

Antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remain challenging. This study aims to explore the best antithrombotic strategy for AF patients after PCI based on a network meta-analysis. This study was registered in PROSPERO (CRD42018093928). The PubMed, Cochrane, and EMBASE databases were searched to identify clinical trials concerning antithrombotic therapy for AF patients with PCI from inception to April 2018. Pairwise and network meta-analysis were conducted to compare clinical outcomes of different antithrombotic therapy. The primary endpoint was major bleeding. Fifteen studies including 16,382 patients were identified with follow-up ranging from 3 to 12 months. Non-vitamin K oral anticoagulants (NOAC) plus P2Y12 inhibitor ranked first with a reduced risk of major bleeding compared with vitamin K antagonist (VKA) plus dual antiplatelet therapy (OR: 0.57, 95% CI: 0.43-0.75) but with no significant difference compared with VKA plus single platelet therapy (OR: 0.85, 95% CI: 0.62-1.16). Similar thrombotic events were evident among these groups. Subgroup analysis showed that VKA plus aspirin exhibited a similar risk of major bleeding compared with VKA plus clopidogrel (OR: 0.94, 95% CI: 0.73-1.23) but was associated with increased risks of ischaemic stroke (OR: 2.10, 95% CI: 1.33-3.32) and all-cause death (OR: 1.77, 95% CI: 1.15-2.74) versus VKA plus clopidogrel. In AF patients undergoing PCI, NOAC plus P2Y12 inhibitor and VKA plus clopidogrel, but not VKA plus aspirin, were associated with reduced risk of major bleeding compared with the recommended VKA-based triple therapy, while thrombotic events were similar among these treatments.


Assuntos
Fibrilação Atrial/cirurgia , Fibrinolíticos/efeitos adversos , Hemorragia/epidemiologia , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Estudos Observacionais como Assunto , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina K/antagonistas & inibidores
8.
Med Sci Monit ; 25: 2649-2657, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971681

RESUMO

BACKGROUND Oral anticoagulants (OACs) such as warfarin and non-VKA oral anticoagulants (NOACs) have been recommended for patients with atrial fibrillation (AF) who are at risk for stroke. Whether NOACs have a higher persistence than warfarin is still unclear. This is especially true in China. MATERIAL AND METHODS Data from a large hospital-based cohort in China (China-AF Registry) from 2011 to 2017 were used for this study. Non-valvular AF patients with newly initiated OACs were included. A time-to-event approach was used to analyze patient persistence. The survival distributions of persistence were compared using the log-rank test. A multivariable Cox regression model was used to explore predictors of warfarin and NOACs non-persistence. RESULTS Patients with newly initiated warfarin (n=4845) or NOACs (n=854) were included in this study. Persistence rates at 1, 2, and 3 years were 93.2%, 89.4%, and 87.2% in the warfarin group and 88.8%, 84.3%, and 81.3% in the NOAC group respectively. Non-persistence was significantly higher with NOACs than with warfarin. On multivariate analysis, age <75 years old, outpatient clinic visits, asymptomatic AF, paroxysmal AF, duration of AF <3 years, history of peptic ulcer, and no previous TIA, stroke or thromboembolism were strong predictors of warfarin non-persistence, while in the NOACs group, age <75 years old, outpatient clinic visits, lower education status and no history of congestive heart failure were predictors. CONCLUSIONS Treatment persistence of NOACs was lower than that of warfarin among Chinese patients with AF. Patients with characteristics of non-persistence predictors need special attention to maintain their therapy.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Adesão à Medicação , Sistema de Registros , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêutico , Idoso , Anticoagulantes/farmacologia , China , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Varfarina/farmacologia
9.
Expert Opin Drug Metab Toxicol ; 15(5): 381-398, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30951640

RESUMO

INTRODUCTION: The availability of non-vitamin K antagonist oral anti-coagulants alongside vitamin K antagonists has offered a variety of options for anti-coagulation, but has also necessitated a good understanding of the pharmacological properties of each of these drugs prior to their use, to maximise the therapeutic benefit and minimise patient harm Areas covered: This review article outlines the pharmacokinetic and pharmacodynamic profiles of the currently licensed VKAs and NOACs that are most commonly used in clinical practice, with the aim of demonstrating how variations in these characteristics influence their use in clinical practice. A literature search was conducted on PubMed using keywords and relevant articles published by the 31st of December 2018 were included. Expert opinion: The effect of a drug is determined by a combination of elements which include patient characteristics and external factors, in addition to its pharmacokinetic and pharmacodynamic properties. A good understanding of these is essential. Despite the wealth of information available, particularly on VKAs, our knowledge on the pharmacology responsible for certain drug effects and inter-individual variations is still limited. Increasing efforts are being made to understand these and include focus on pharmacogenomics and drug transporter proteins.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Administração Oral , Animais , Anticoagulantes/farmacocinética , Anticoagulantes/farmacologia , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Farmacogenética/métodos
10.
Scand J Trauma Resusc Emerg Med ; 27(1): 48, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014373

RESUMO

BACKGROUND: Prothrombin complex concentrate (PCC) is widely used to reverse the action of direct oral anticoagulants (DOACs) in accordance with current guidelines and because of a lack of specific reversal agents. Indications, clinical characteristics and patient outcomes of patients might differ in comparison to reversal of vitamin K antagonists where reversal with PCC is well established. METHODS: Our cohort study explores patient characteristics, indications and clinical outcomes for reversal of all DOAC patients receiving PCC at our university emergency department from 01.06.2012 to 01.07.2017, in comparison with patients on VKA. RESULTS: Out of 199,982 consultations, we studied 346 patients who were given PCC for reversal of either DOAC (n = 74) or VKA (n = 272). The most common reason for treatment was acute bleeding; in 86.7% of both groups. 37.3% of bleeding was traumatic (p = 0.666). The most frequent bleeding location was intracranial (61.6%, p = 0.881). Gastrointestinal bleeding was more often found in the DOAC group (18.9% vs. 8.8%, p = 0.014). More erythrocyte concentrates (ECs) were given to DOAC patients with blood transfusion (p = 0.014). Tranexamic acid was used more often in DOAC patients than in VKA patients (28.4% vs. 7.4%, p < 0.001). No significant group differences were found for the following patient outcomes: in-hospital mortality, ICU stay, and length of stay at the ICU or in hospital. CONCLUSION: In DOAC treated patients, PCC was applied more often because of gastrointestinal bleeding and patients received higher numbers of ECs as well as tranexamic acid. No differences were observed with regard to important clinical outcomes.


Assuntos
Anticoagulantes/administração & dosagem , Fatores de Coagulação Sanguínea/administração & dosagem , Hemorragia/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Doença Aguda , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Seguimentos , Hemorragia/mortalidade , Mortalidade Hospitalar/tendências , Humanos , Masculino , Conduta do Tratamento Medicamentoso , Estudos Retrospectivos , Suíça/epidemiologia , Resultado do Tratamento
11.
J Stroke Cerebrovasc Dis ; 28(7): 1918-1925, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005561

RESUMO

BACKGROUND: Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months. METHODS: This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups. RESULTS: The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs. DISCUSSION: This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Hemorragias Intracranianas/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Feminino , Humanos , Incidência , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/epidemiologia , Japão/epidemiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Varfarina/efeitos adversos
12.
J Physiol Pharmacol ; 70(1)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31019123

RESUMO

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.


Assuntos
Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Fibrina , Rivaroxabana/uso terapêutico , Trombose/fisiopatologia , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêutico , Adulto , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/fisiopatologia , Viscosidade
13.
Orv Hetil ; 160(13): 509-515, 2019 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-30907102

RESUMO

INTRODUCTION: In the treatment of non-valvular atrial fibrillation (AF) with oral anticoagulants (OAC), medical adherence is a relevant factor for stroke prevention. AIM: To evaluate the one-year persistence of vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC) in patients suffering from AF and already treated with OACs. METHOD: Information from the National Health Insurance Fund of Hungary prescriptions database on pharmacy claims between June 1, 2015 and December 31, 2015 was analysed. Authors identified patients who filled prescriptions for OACs (VKAs or DOACs) prescribed for AF who have already received OACs therapy during one year before. Apparatus of survival analysis was used, where 'survival' was the time to abandon the medication. RESULTS: 196 016 patients met the inclusion criteria. 181 810 patients received VKA and 14 206 patients were treated with DOACs. The one-year persistence rate in patients taking VKA was 52.9% whereas it was 66.8% in those on the DOACs. The persistence rates after 360 days were 67.5% for rivaroxaban, 63.6% for apixaban and 63.4% for dabigatran. The mean duration of persistence was 311 days for rivaroxaban, 308 days for apixaban and 284 days for dabigatran. The actual rate of discontinuation was 14% (HR = 1.14 [95% CI 1.05-1.24]), p = 0.0015) for apixaban, 15% (HR = 1.15 [95% CI 1.08-1.23], p = 0.003) for dabigatran and 62% (HR = 1.62 [95% CI 1.56-1.69], p<0.0001) for VKA compared to rivaroxaban (reference). CONCLUSIONS: The authors have confirmed that the one-year persistence of DOAKs was significantly higher compared to KVA therapy in AF. The one-year persistence of rivaroxaban was more favoured than apixaban and dabigatran. Orv Hetil. 2019; 160(13): 509-515.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Administração Oral , Dabigatrana/administração & dosagem , Bases de Dados Factuais , Humanos , Hungria , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Resultado do Tratamento , Vitamina K/antagonistas & inibidores
14.
Biomed Res Int ; 2019: 5473240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30895193

RESUMO

Background: Combination of dual antiplatelet (DAPT) and oral anticoagulation therapy is required to decrease cardioembolic stroke and stent thrombosis risk in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). We compared the safety and efficacy of dabigatran etexilate with vitamin K antagonist (VKA), in combination with DAPT (aspirin plus clopidogrel) treatment in AF patients who underwent percutaneous coronary intervention (PCI) with stenting for ACS. Methods: Consecutive nonvalvular AF patients who received twice-daily dabigatran 110 mg (n = 389) or VKA (n = 510) and DAPT were included. Primary endpoints were major bleeding (safety) and the composite of ischemic stroke, systemic embolism, and myocardial infarction (efficacy). The secondary efficacy endpoint was hospitalization for cardiovascular disease. Results: After propensity score matching, comparative treatment groups comprised 175 dabigatran recipients and 175 VKA recipients. The cumulative incidence of major bleeding was lower in the dabigatran group (2.3%) compared with the VKA group (10.3%) with a hazard ratio (HR) of 4.81 [95% confidence interval (CI) 1.6-14.2, p < 0.005]. The cumulative incidence of thromboembolic events with dabigatran was slightly higher (8.0%) than with VKA (6.85%), but not statistically significantly so (0.8, 0.39-1.8; p = 0.6). Cumulative incidence of hospitalization for cardiovascular disease was lower with dabigatran (10.3%) compared with VKA (20.6%) treatment (2.2, 1.25-3.8; p < 0.006). Conclusion: Dabigatran at the dose used for stroke prevention appears safer than VKA and maintains a similar efficacy profile, when used with DAPT, in AF patients who have undergone PCI with stenting for ACS.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Vitamina K/antagonistas & inibidores , Idoso , Quimioterapia Combinada , Feminino , Hemorragia/etiologia , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Adesão à Medicação , Projetos Piloto , Probabilidade , Pontuação de Propensão , Tromboembolia/etiologia , Resultado do Tratamento
16.
Clin Appl Thromb Hemost ; 25: 1076029619837362, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30907120

RESUMO

Patients receiving durable mechanical circulatory support (MCS) require life-long anticoagulation with a vitamin K antagonist (VKA). Due to alternations in hemostasis, concomitant therapy with antiplatelet agents and critical illness, they are at increased risk of thromboembolic and bleeding complications compared with the general population managed on VKAs. To prevent thrombotic events, current guidelines recommend that patients with MCS receive long-term anticoagulation with a VKA to maintain a target international normalized ratio (INR) as specified by device manufacturers, but limited data exist regarding specific routine management of anticoagulation therapy and its potential complications. To optimize anticoagulation management and minimize risk in these patients, we have centralized anticoagulation management in a collaborative approach between the inpatient hemostatic and antithrombotic (HAT) stewardship service and between ambulatory anticoagulation management service (AMS) and the advanced heart disease team. Patients are followed by these three services beginning when the device is implanted and extending the duration that patients have the device. The teams include multiple clinicians from cardiac surgery, cardiology, hematology, pharmacy, nursing, case management, nutrition, and psychiatry, therefore, in order to standardize practice among clinicians without compromising patient centered decision making, we assembled an interdisciplinary team to create multiple treatment guidelines. In addition to a centralized and collaborative approach, our guidelines ensure seamless transitions of care between the inpatient and outpatient settings. We believe our approach has demontrated a positive improvement in the care of these challenging patients. In this article, we present our comprehensive centralized anticoagulation management approach for patients with left ventricular assist systems (LVAS).


Assuntos
Anticoagulantes/administração & dosagem , Coeficiente Internacional Normatizado , Tromboembolia , Trombose , Vitamina K/antagonistas & inibidores , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Tromboembolia/sangue , Tromboembolia/tratamento farmacológico , Trombose/sangue , Trombose/tratamento farmacológico
17.
N Engl J Med ; 380(16): 1509-1524, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883055

RESUMO

BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).


Assuntos
Síndrome Coronariana Aguda/complicações , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Pirazóis/efeitos adversos , Piridonas/efeitos adversos
18.
Crit Care ; 23(1): 62, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30795779

RESUMO

There is a high degree of uncertainty regarding optimum care of patients with potential or known intake of oral anticoagulants and traumatic brain injury (TBI). Anticoagulation therapy aggravates the risk of intracerebral hemorrhage but, on the other hand, patients take anticoagulants because of an underlying prothrombotic risk, and this could be increased following trauma. Treatment decisions must be taken with due consideration of both these risks. An interdisciplinary group of Austrian experts was convened to develop recommendations for best clinical practice. The aim was to provide pragmatic, clear, and easy-to-follow clinical guidance for coagulation management in adult patients with TBI and potential or known intake of platelet inhibitors, vitamin K antagonists, or non-vitamin K antagonist oral anticoagulants. Diagnosis, coagulation testing, and reversal of anticoagulation were considered as key steps upon presentation. Post-trauma management (prophylaxis for thromboembolism and resumption of long-term anticoagulation therapy) was also explored. The lack of robust evidence on which to base treatment recommendations highlights the need for randomized controlled trials in this setting.


Assuntos
Anticoagulantes/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Administração Oral , Anticoagulantes/efeitos adversos , Áustria , Lesões Encefálicas Traumáticas/fisiopatologia , Consenso , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Desamino Arginina Vasopressina/farmacologia , Humanos , Comunicação Interdisciplinar , Tempo de Tromboplastina Parcial/métodos , Pirazóis/análise , Pirazóis/sangue , Pirazóis/uso terapêutico , Piridinas/análise , Piridinas/sangue , Piridinas/uso terapêutico , Piridonas/análise , Piridonas/sangue , Piridonas/uso terapêutico , Rivaroxabana/análise , Rivaroxabana/sangue , Rivaroxabana/uso terapêutico , Tiazóis/análise , Tiazóis/sangue , Tiazóis/uso terapêutico , Tromboembolia/prevenção & controle , Tomografia Computadorizada por Raios X/métodos , Ácido Tranexâmico/uso terapêutico , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Vitamina K/uso terapêutico
19.
J Korean Med Sci ; 34(6): e52, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30787683

RESUMO

Cancer-associated venous thromboembolism (CAT) is a common complication associated with high morbidity and mortality. In accordance with major clinical trials comparing low-molecular-weight heparin (LMWH) with a vitamin K antagonist (VKA), LMWH is currently the standard treatment for CAT, owing to its efficacy for thrombosis recurrence and improved safety profile compared to VKA. Over the past few years, direct oral anticoagulants (DOACs) have emerged as potential alternative therapies to LMWH due to their convenient route of administration and predictable pharmacokinetics, but evidence for their use in CAT is inconclusive, as only a small fraction of the study populations in these trials had CAT. Recently, two large head-to-head trials comparing DOACs to LMWH in CAT patients reported comparable efficacies of DOACs with increased bleeding risk. Occasionally, CAT treatment can be challenging due to the heterogeneity of underlying malignancies and comorbidities. Renal insufficiency and gastrointestinal defects are the main obstacles in anticoagulant selection. Careful choice of treatment candidates and proper anticoagulant strategies are critical for the treatment of CAT; hence, more studies are required to address these challenges.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/patologia , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Ensaios Clínicos como Assunto , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/complicações , Insuficiência Renal/complicações , Insuficiência Renal/patologia , Fatores de Risco , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/patologia , Vitamina K/antagonistas & inibidores
20.
Semin Thromb Hemost ; 45(2): 171-179, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30743279

RESUMO

For procedures associated with minimal bleeding risk, there are data and experience to support the practice of continuing vitamin K antagonists rather than interrupting therapy, to prevent exposing patients to the undue risk of developing thromboembolism during anticoagulation cessation. Despite the increasing use of non-vitamin K oral anticoagulants (NOACs), there is little evidence to guide the management of these drugs around minimal bleeding risk procedures. This review examines and discusses the major society guidelines and recommendations addressing the management of NOACs around minimal bleeding risk procedures. Additionally, it summarizes the existing evidence, and highlights the gaps in knowledge where evidence is not yet available. Finally, recommendations are made to assist the proceduralist deal with this area of limited evidence.


Assuntos
Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Guias de Prática Clínica como Assunto , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Humanos , Fatores de Risco , Tromboembolia Venosa/prevenção & controle , Vitamina K/antagonistas & inibidores
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