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1.
Cancer Treat Res ; 179: 103-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317483

RESUMO

The management of cancer-associated thrombosis (CAT) is complex, and treatment strategies have been evolving over the past 15 years. It is well recognized that oral vitamin K antagonists are difficult to use in cancer patients, with higher rates of treatment failure and bleeding complications than in non-cancer patients. Low-molecular-weight-heparin (LMWH) became the widely accepted standard of care for treatment of cancer-associated thrombosis, following the CLOT study comparing dalteparin with warfarin in 2003. LMWH remains widely used for the treatment of CAT. However, in the past two years, several studies have served to validate direct oral anticoagulants as a safe and effective alternative to LMWH. Two randomized clinical trials comparing edoxaban and rivaroxaban with dalteparin, and several retrospective studies have shown the efficacy of edoxaban and rivaroxaban for the treatment of CAT. However, there is an evidence of increased bleeding with the DOACs, particularly gastrointestinal or urinary tract bleeding in patients with lesions within the gastrointestinal or urinary tracts. This chapter discusses the ongoing development of optimal treatment strategies for cancer-associated thrombosis.


Assuntos
Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Tromboembolia Venosa/etiologia
2.
Hosp Pract (1995) ; 47(3): 113-122, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31317796

RESUMO

Direct oral anticoagulants (DOACs) include dabigatran etexilate, a direct thrombin inhibitor, and specific inhibitors of activated coagulation factor X (FXa; e.g. apixaban, betrixaban, edoxaban, rivaroxaban). DOACs are associated with lower rates of major and fatal bleeding events compared with warfarin. Clinicians may need to achieve rapid reversal of anticoagulation effects of the DOACs in an emergency setting. Idarucizumab and andexanet alfa, which reverse the anticoagulant effects of dabigatran and FXa inhibitors, respectively, are DOAC reversal agents available in the US. Other reversal agents (e.g. ciraparantag for heparins, DOACs) are in development. Alternative nonspecific agents (e.g. fresh frozen plasma, prothrombin complex concentrate) are available. Nonspecific prohemostatic agents can counteract the anticoagulant action of DOACs in emergency situations, when specific reversal agents are unavailable. However, specific reversal agents are efficacious and safe and should be preferred when available. In this review, we discuss practical issues in the initiation of DOAC therapy, situations where reversal may be needed, coagulation assays, reversal agents, and post-reversal complications in the context of published evidence and guidelines.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticoagulantes/administração & dosagem , Antitrombinas/uso terapêutico , Dabigatrana/antagonistas & inibidores , Fator X/antagonistas & inibidores , Fator Xa/farmacologia , Pacientes Internados , Proteínas Recombinantes/farmacologia , Administração Oral , Coagulação Sanguínea/efeitos dos fármacos , Serviços Médicos de Emergência , Fator Xa/agonistas , Inibidores do Fator Xa/uso terapêutico , Hemorragia/tratamento farmacológico , Humanos , Corpo Clínico Hospitalar
3.
Khirurgiia (Mosk) ; (5): 94-103, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31169827

RESUMO

The review is devoted to the issue of optimal duration of anticoagulant therapy for venous thromboembolic complications (VTEC) using oral anticoagulants (OAC). These drugs are characterized by higher safety in comparison with vitamin K antagonists and make it possible to increase the duration of treatment for not only spontaneous thrombosis (with high risk of recurrence), but also thrombosis provoked by minor persistent and transient risk factors of VTEC. Efficacy and safety of prolonged treatment of VTEC using OAC was analyzed. Different classifications of primary thrombotic episode depending on risk of subsequent recurrence are presented. Moreover, scales for individual assessment of risk of recurrent thrombosis after anticoagulant therapy cancellation and risk of bleeding in case of continued treatment are given. Outcomes of long-term administration of rivaroxaban for VTEC are analyzed. It was concluded that OAC are safe for prolonged management of primary thrombotic episode. However, overall duration of treatment should be determined considering individual balance of benefits and risks.


Assuntos
Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Esquema de Medicação , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Recidiva , Fatores de Risco , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Trombose/etiologia , Fatores de Tempo , Suspensão de Tratamento
4.
J Stroke Cerebrovasc Dis ; 28(8): 2273-2279, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160218

RESUMO

BACKGROUND: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Embolia Intracraniana/tratamento farmacológico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(20): e15705, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096518

RESUMO

RATIONALE: Rivaroxaban has numerous advantages over traditional anticoagulation therapy. Fixed doses can be administered without requiring routine monitoring of coagulation, and anticoagulation efficacy is more predictable. Safety, including fewer drug interactions, and reduced bleeding, is also improved with rivaroxaban based on current recommendations. The goal of this report was to explore if low-dose rivaroxaban 10 mg once daily was effective in an elderly patient who developed minor bleeding when treated with rivaroxaban (10 mg twice daily) for a pulmonary embolism. PATIENT CONCERNS: We present an 88-year-old female with dyspnea and fatigue, which became increasingly worse over a month in the absence of medication. Her weight was 64 kg. Routine coagulation assays and renal function were normal at time of admission. DIAGNOSIS: Deep vein thrombosis and pulmonary embolism were confirmed by venous compression ultrasonography and computed tomography pulmonary angiography. INTERVENTIONS: Oral rivaroxaban 10 mg twice daily was administered, but the patient developed hemoptysis and gum bleeding 5 days later. The dose of rivaroxaban was reduced to 10 mg once daily, and bleeding gradually disappeared after 3 days. OUTCOME: At follow-up 90 days after treatment, the patient reported no discomfort. Venous compression ultrasonography and computed tomography pulmonary angiography showed normal results; therefore, treatment was terminated. LESSONS: Elderly patients exhibit variable tolerance of anticoagulants, warranting careful consideration of the risk of bleeding. Low-dose rivaroxaban was an effective treatment for pulmonary embolism in the elderly patient presented here.


Assuntos
Embolia Pulmonar/tratamento farmacológico , Rivaroxabana/uso terapêutico , Trombose Venosa/tratamento farmacológico , Administração Oral , Assistência ao Convalescente , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada/métodos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Embolia Pulmonar/diagnóstico por imagem , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento , Ultrassonografia/métodos , Trombose Venosa/diagnóstico por imagem
6.
J Stroke Cerebrovasc Dis ; 28(7): e100-e101, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31006519

RESUMO

Pulmonary arteriovenous fistula (PAVF), a vessel malformation connecting the pulmonary circulation to the systemic circulation while bypassing the pulmonary capillaries, can cause paradoxical cerebral infarction. It is often associated with hereditary hemorrhagic telangiectasia (HHT), a genetic disease characterized by multiple dermal, mucosal, and visceral telangiectasia causing recurrent bleeding. Paradoxical cerebral embolism caused by PAVF without HHT is rare. Here, we report a patient with isolated PAVF who experienced an ischemic stroke caused by a paradoxical embolism from deep venous thrombosis; the patient was successfully treated with recombinant tissue plasminogen activator. She presented with a decrease in arterial oxygen saturation to 91%, and lung disease was suspected. A PAVF was subsequently found in the right S6 region using contrast computed tomography. Interventional radiologists successfully occluded the shunt using 6 microcoils. PAVF should be considered when determining the pathogenesis of cerebral ischemia in patients with hypoxia, which can be the only symptom of PAVF.


Assuntos
Fístula Arteriovenosa/complicações , Embolia Paradoxal/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Embolia Intracraniana/tratamento farmacológico , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Trombose Venosa/complicações , Idoso de 80 Anos ou mais , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Embolia Paradoxal/diagnóstico por imagem , Embolia Paradoxal/etiologia , Embolização Terapêutica/instrumentação , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/diagnóstico por imagem , Angiografia por Ressonância Magnética , Artéria Pulmonar/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Piridinas/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Tiazóis/uso terapêutico , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico
7.
Medicine (Baltimore) ; 98(16): e15224, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31008951

RESUMO

BACKGROUND: Previous clinical trials have addressed that rivaroxaban is effective for the treatment of patients with pulmonary embolism (PE). This study will systematically assess its efficacy and safety for PE. METHODS: We will carry out this study by searching the following electronic databases from inception to March 1, 2019 without language restrictions: Cochrane Library, EMBASE, PUBMED, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. In addition, we will also search clinical trial registries, dissertations, and conference abstracts to avoid any missing potential studies. All randomized controlled trials of rivaroxaban for patients with PE will be fully considered. Two researchers will independently perform literature selection, data collection, and methodological quality assessment. If it is appropriate, outcome data will be pooled by using a fixed-effect model or random-effect model, and meta-analysis will be considered for operation. RESULTS: All efficacy and safety of rivaroxaban for PE will be assessed through all primary and secondary outcomes. The primary outcomes are all-cause mortality and major bleeding. The secondary outcomes are recurrent venous thromboembolism, duration of hospital stay, quality of life, patient satisfaction, and adverse events. CONCLUSION: The findings of this study will summarize updated evidence on the efficacy and safety of rivaroxaban for patients with PE. ETHICS AND DISSEMINATION: It is not necessary to inquire ethical approval for this study, because it will not analyze any individual patient data. The results of this study will be published through peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019126095.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Rivaroxabana/uso terapêutico , Humanos
8.
Gastroenterology ; 157(1): 34-43.e1, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986390

RESUMO

DESCRIPTION: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis. METHODS: This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors. BEST PRACTICE ADVICE 1: Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels. BEST PRACTICE ADVICE 2: In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction-induced coagulation abnormalities. BEST PRACTICE ADVICE 3: Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions. BEST PRACTICE ADVICE 4: The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence. BEST PRACTICE ADVICE 5: Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels. BEST PRACTICE ADVICE 6: The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly. BEST PRACTICE ADVICE 7: The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited. BEST PRACTICE ADVICE 8: Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi. BEST PRACTICE ADVICE 9: Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure. BEST PRACTICE ADVICE 10: Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor). BEST PRACTICE ADVICE 11: Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone. BEST PRACTICE ADVICE 12: Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue/métodos , Cirrose Hepática/sangue , Trombofilia/terapia , Trombose Venosa/terapia , Anticoagulantes/uso terapêutico , Antifibrinolíticos/uso terapêutico , Antitrombinas/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Fatores de Coagulação Sanguínea/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Fibrinogênio/metabolismo , Hematócrito , Heparina/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Cirrose Hepática/complicações , Plasma , Contagem de Plaquetas , Veia Porta , Tromboelastografia , Trombocitopenia , Trombofilia/sangue , Trombofilia/complicações , Trombopoetina/agonistas , Reação Transfusional , Trombose Venosa/sangue , Trombose Venosa/complicações
9.
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
11.
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
13.
Expert Rev Cardiovasc Ther ; 17(4): 319-330, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30897988

RESUMO

INTRODUCTION: Edoxaban is the last direct oral anticoagulant marketed for the prevention of stroke among patients with nonvalvular atrial fibrillation (AF). Areas covered: ENGAGE AF-TIMI 48 was the pivotal clinical trial that led to the approval of edoxaban 60 mg once daily. After the publication of this study, a great number of substudies and post hoc analyses have been published, together with some observational studies. The aim of this review was to update the current evidence about the use of edoxaban in AF patients. Expert opinion: In the ENGAGE AF-TIMI 48 trial, edoxaban 60 mg was noninferior to warfarin for the prevention of stroke or systemic embolism, but significantly reduced the risk of bleeding, major adverse cardiac events and death from cardiovascular causes. The relative efficacy and safety of edoxaban 60 mg compared with warfarin were independent of different clinical conditions, such as prior stroke, age, risk of falls, renal function, hepatic disease, ischemic heart disease, heart failure, valvular heart disease, or cancer. Data about the effectiveness and safety of edoxaban in real-life patients are scarce, but consistent with those of the pivotal clinical trial. Edoxaban seems a cost-effective alternative to warfarin among AF patients with moderate to high thromboembolic risk.


Assuntos
Fibrilação Atrial/complicações , Inibidores do Fator Xa/uso terapêutico , Piridinas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Tiazóis/uso terapêutico , Tromboembolia/prevenção & controle , Anticoagulantes/uso terapêutico , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Inibidores do Fator Xa/farmacocinética , Hemorragia/induzido quimicamente , Humanos , Piridinas/farmacocinética , Acidente Vascular Cerebral/etiologia , Tiazóis/farmacocinética , Tromboembolia/etiologia , Varfarina/uso terapêutico
14.
Expert Opin Drug Saf ; 18(4): 313-320, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30925842

RESUMO

INTRODUCTION: Cancer patients with cancer-associated thrombosis (CAT) are at an elevated risk of recurrent venous thromboembolism (VTE) and of major bleeding while receiving treatment with anticoagulation. Recently, Xa inhibitors have been assessed in cancer patients for the treatment of CAT, providing clinicians and patients with more treatment options. AREAS COVERED: In this narrative review, the authors evaluate the evidence regarding the efficacy and safety of edoxaban, rivaroxaban, and apixaban in the treatment of CAT. EXPERT OPINION: Xa inhibitors are an effective, safe, and convenient option for the treatment of CAT. Overall, they may be associated with a lower risk of recurrent VTE in cancer patients. Certain subgroups of cancer patients may be at increased risk of major bleeding while on treatment with Xa inhibitors, when compared to low-molecular-weight-heparin (LMWH). The current published data suggests an increase in gastrointestinal (GI) major bleeding in patients with GI malignancies. Other patient, treatment, and cancer characteristics may also be associated with a higher risk of major bleeding. Therefore, when assessing the appropriateness of Xa inhibitors for the treatment of CAT, the clinician must take into consideration the known interactions of these drugs, the individualized bleeding risk, and the patient's preferences, in order to make the best possible anticoagulation therapy recommendation.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Tromboembolia Venosa/etiologia
15.
Crit Care Nurs Clin North Am ; 31(1): 77-90, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30736937

RESUMO

The purpose of this article is to educate staff nurses and advanced practice nurses the importance of identifying, diagnosing, and making appropriate clinical decisions when treating patients with atrial fibrillation. Atrial fibrillation is a supraventricular arrhythmia characterized by uncoordinated, chaotic electrical activity and deterioration of proper atrial mechanical function, with an irregular ventricular response. Poorly controlled or undiagnosed atrial fibrillation increases the risk of mortality and may decrease quality of life. Identifying and staying abreast of cardiovascular care and current updates in treatment is strongly encouraged as guidelines are revised and updated as new treatments evolve.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/enfermagem , Enfermagem de Cuidados Críticos , Antitrombinas/uso terapêutico , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Hemorragia/prevenção & controle , Humanos , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle
16.
BMJ Case Rep ; 12(2)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30798276

RESUMO

This 37-year-old man presented with left sided facial warmth and numbness associated with new sudden-onset right hemiparesis. The patient first developed sudden numbness of his left lip and warmth in left ear which travelled to the rest of left face. His past medical history was significant for hypertension, Hodgkin lymphoma treated with radiation therapy at the age of 10, and sleeve gastrectomy for obesity 1 year ago complicated by bilateral ischaemic cerebral infarctions with residual left hemiparesis. No acute infarcts were found on MRI. Transesophageal echocardiography revealed a complex atheroma near the sinotubular junction in ascending aorta.


Assuntos
Valva Aórtica/fisiologia , Doenças das Valvas Cardíacas/diagnóstico , Paresia/etiologia , Acidente Vascular Cerebral/diagnóstico , Adulto , Anticolesterolemiantes/uso terapêutico , Valva Aórtica/diagnóstico por imagem , Aspirina/uso terapêutico , Ecocardiografia Transesofagiana , Inibidores do Fator Xa/uso terapêutico , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Paresia/fisiopatologia , Rivaroxabana/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
17.
Knee ; 26(2): 451-458, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30700390

RESUMO

BACKGROUND: Anticoagulants are used following total knee arthroplasty (TKA) to prevent venous thromboembolism (VTE). These drugs reduce VTE risk but may lead to bleeding-related complications. Recently, surgeons have advocated using antiplatelet agents including aspirin (ASA). However, there is no consensus regarding which medication has the optimal risk/benefit profile. The purpose of this study was to compare rates of VTE using different anticoagulants in anticoagulation-naïve patients being discharged home after TKA. METHODS: A national private insurance database was used to identify patients undergoing unilateral TKA. Patients with a prior history of VTE were excluded. Anticoagulants included ASA, low molecular weight heparin (LMWH), warfarin, factor Xa inhibitors (XaI), and fondaparinux. Postoperative complications, including VTE, blood transfusion, myocardial infarction, and hematoma, were identified using ICD-9 diagnosis codes. Risk of each complication was compared between groups using multivariate logistic regression controlling for demographics, length of stay, and comorbidities. RESULTS: Of 30,813 patients, 1.82% were diagnosed with VTE. Using ASA as a baseline, there was significantly decreased risk of VTE with LMWH (OR 0.47), XaI (OR 0.50), and fondaparinux (OR 0.32). There was significantly higher risk of transfusion with LMWH (OR 1.56) and fondaparinux (OR 1.84), but no difference in hematoma between medications. CONCLUSIONS: This study shows that there is a decreased risk of VTE with LMWH, XaI, and fondaparinux compared to ASA. However, these medications also had higher rates of bleeding-associated complications. The choice of pharmacologic prophylaxis should be made based on a balance of the risk/benefit profile of each medication. LEVEL OF EVIDENCE: III.


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Quimioprevenção/métodos , Bases de Dados Factuais , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Fondaparinux/efeitos adversos , Fondaparinux/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Medição de Risco , Tromboembolia Venosa/etiologia , Varfarina/efeitos adversos , Varfarina/uso terapêutico
18.
J Stroke Cerebrovasc Dis ; 28(5): e39-e43, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30772162

RESUMO

BACKGROUND: Cerebral venous thrombosis is rare and an uncommon cause of stroke and has diverse etiologies and varied clinical presentations. Here, we report 2 cases of deep cerebral venous thrombosis. CASE DESCRIPTION: A 64-year-old woman presented with cerebral venous thrombosis due to a hypercoagulable state associated with ovarian tumor. On initial fluid-attenuated inversion recovery and diffusion-weighted imaging, there was a diffuse high-intensity lesion in the bilateral thalamus. Computed tomography angiography showed occlusion of the straight sinus, vein of Galen, and internal cerebral vein. Single-photon emission computed tomography showed decreased cerebral blood flow in the bilateral thalamus. After 3 weeks of factor Xa inhibitor therapy, the patient's consciousness gradually improved and eventually became clear enough to leave the hospital. She had no neurological deficit. Another patient was a 47-year-old man who presented with splitting headache and drowsiness. Magnetic resonance venography confirmed deep thrombosis of the vein of Galen. He completely recovered after 4 weeks of factor Xa inhibitor therapy. CONCLUSIONS: This study reports on 2 rare cases of decreased cerebral blood flow in the bilateral thalamus on single-photon emission computed tomography, which improved following the administration of factor Xa inhibitor.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Inibidores do Fator Xa/uso terapêutico , Trombose Intracraniana/tratamento farmacológico , Piridinas/uso terapêutico , Tálamo/irrigação sanguínea , Tiazóis/uso terapêutico , Trombose Venosa/cirurgia , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Flebografia , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/fisiopatologia
19.
Bone Joint J ; 101-B(2): 207-212, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30700116

RESUMO

AIMS: Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis. The secondary aim was to assess the non-inferiority of the reduction of blood loss of the short protocol versus the long protocol. PATIENTS AND METHODS: A multicentre, prospective, randomized, double-blind, placebo-controlled trial was undertaken involving 229 patients undergoing primary cementless THA using a posterior approach, whose extended rivaroxaban thromboprophylaxis started on the day of surgery. There were 98 male and 131 female patients, with a mean age of 65.5 years (32 to 91). The primary outcome, perioperative RBL, was evaluated at 72 hours postoperatively. The efficacy of short- and long-TXA protocols in the reduction of perioperative RBL was compared with a placebo group. RESULTS: TXA significantly reduced perioperative blood loss compared with placebo (p < 0.001); the mean differences were 525.3 ml (short-TXA vs placebo) and 550.1 ml (long-TXA vs placebo). No venous or arterial thromboembolic complications were reported. The upper boundary of the 95% confidence interval, when comparing short and long protocols, was below the pre-specified margin of non-inferiority (p = 0.027). CONCLUSION: In patients undergoing primary cementless THA, using a posterior approach, who are treated with rivaroxaban for thromboembolic prophylaxis, short- and long-TXA IV protocols are significantly more effective than placebo in reducing perioperative RBL, without any thromboembolic complications. Non-inferiority of a short- versus a long-TXA protocol in reducing perioperative RBL was supported in a secondary analysis.


Assuntos
Artroplastia de Quadril , Perda Sanguínea Cirúrgica/prevenção & controle , Fármacos Hematológicos/uso terapêutico , Artropatias/cirurgia , Rivaroxabana/uso terapêutico , Ácido Tranexâmico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/uso terapêutico , Cimentos para Ossos , Cimentação , Quimioprevenção , Método Duplo-Cego , Inibidores do Fator Xa/uso terapêutico , Feminino , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
20.
Thromb Res ; 175: 53-58, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30708169

RESUMO

BACKGROUND: No study supports the use of either aPTT or anti-Xa activity for heparin monitoring in critical care patients. There are no strong data on the agreement between aPTT and anti-Xa. The aims of this study were to: 1. Analyse the agreement between aPTT and anti-Xa in a large population of critically ill patients under unfractionated heparin therapy (UFH), 2. Identify clinical and biological factors associated to agreement or disagreement, and 3. Analyse the impact of anti-Xa availability on the use of aPTT and UFH therapy. METHODS: Retrospective study in a 35 beds mixed-ICU population between 2006 and 2016 in a University teaching hospital. INCLUSION CRITERIA: delivery of a UFH dose >15,000 U/24 h during at least one day with one anti-Xa determination. DATA: demographic variables, aPTT, anti-Xa, laboratory variables, presence of extracorporeal devices (ECD). Pairs of simultaneously dosed aPTT and anti-Xa [aPTT:anti-Xa] were analysed on the basis of their agreement within the sub-therapeutic, therapeutic (aPTT 50-80″, anti-Xa 0.3-0.7 U/ml) or supra-therapeutic ranges. RESULTS: 2283 patient admissions (2085 patients) were analysed. 35,595 [aPTT:anti-Xa] pairs were found. The overall [aPTT:anti-Xa] agreement was 59.6% and lowest (54.3%) in presence of ECD compared to non-ECD patients (61.6%; p < 0.001). Sixteen demographic and biological variables were analysed and were not predictive of [aPTT:anti-Xa] agreement. No significant difference in administered UFH dose was observed after anti-Xa introduction. CONCLUSION: In this large cohort, the [aPTT:anti-Xa] agreement is <60% and significantly lower in patients with ECD. None of the variables identified as potentially affecting the agreement were predictive. Availability of anti-Xa had neither effect on aPTT use nor on UFH-dose. These results call for a prospective study to determine the optimal UFH-therapy monitoring tool.


Assuntos
Anticoagulantes/sangue , Inibidores do Fator Xa/uso terapêutico , Heparina/sangue , Tempo de Tromboplastina Parcial/métodos , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Estudos de Coortes , Estado Terminal , Inibidores do Fator Xa/farmacologia , Feminino , Heparina/farmacologia , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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