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1.
Medicine (Baltimore) ; 100(12): e24522, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761634

RESUMO

BACKGROUND: The intracranial hemorrhage (ICH) risk of oral anticoagulants/non-vitamin K antagonist oral anticoagulants (NOACs) remains largely unknown. Patients who need oral anticoagulants such as aspirin or warfarin often suffer from obvious complications. METHODS: This network meta-analysis intended to assess the ICH risk in patients taking NOACs. The data from PubMed, the Cochrane database, and Embase were reviewed. All phase III randomized controlled trials of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), aspirin and warfarin were reviewed. RESULTS: Twenty-three trials involving 137,713 participants were included, involving 6 regimens. Warfarin had the first risk of ICH (surface under the cumulative ranking area: 0.82), followed by dabigatran, edoxaban, aspirin, apixaban, rivaroxaban, and placebo. Dabigatran had the lowest risk of all-cause mortality (surface under the cumulative ranking area: 0.63), followed by apixaban, edoxaban, warfarin, rivaroxaban, aspirin, and placebo. CONCLUSION: Warfarin significantly increased the risk of ICH in patients taking oral anticoagulants compared with 4 NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) and aspirin. Apixaban is least likely to induce all-cause mortality.


Assuntos
Antitrombinas/efeitos adversos , Aspirina/efeitos adversos , Hemorragias Intracranianas/epidemiologia , Varfarina/efeitos adversos , Administração Oral , Antitrombinas/administração & dosagem , Aspirina/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Humanos , Hemorragias Intracranianas/induzido quimicamente , Mortalidade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco/estatística & dados numéricos , Varfarina/administração & dosagem
2.
BMC Pulm Med ; 21(1): 102, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761886

RESUMO

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a pandemic affecting all countries in the world. Italy has been particularly afflicted by the health emergency, and since the peak phase has passed, major concern regarding medium to long term complications due to COVID-19 is arising. Little is known in literature regarding thromboembolic complications once healed after COVID-19. CASE PRESENTATION: A 51-year-old patient recovered from COVID-19 pneumonia complicated by pulmonary embolism (PE) came to the hospital for palpitations and chest pain. Although he was on treatment dose of direct oral anticoagulation (DOAC), massive recurrent PE was diagnosed. CONCLUSION: In the early post COVID-19 era, the question remains regarding the efficacy of DOACs in COVID-19 patients.


Assuntos
Anticoagulantes/administração & dosagem , Dabigatrana/administração & dosagem , Heparina/administração & dosagem , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/virologia , Varfarina/administração & dosagem , Administração Oral , Anticoagulantes/uso terapêutico , Dabigatrana/uso terapêutico , Quimioterapia Combinada , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/tratamento farmacológico , Recidiva , Varfarina/uso terapêutico
3.
PLoS Comput Biol ; 17(3): e1008805, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33730015

RESUMO

Thrombosis is a recognized complication of Coronavirus disease of 2019 (COVID-19) and is often associated with poor prognosis. There is a well-recognized link between coagulation and inflammation, however, the extent of thrombotic events associated with COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) and Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), which are all proteins linked to coagulation, have been shown to interact with SARS proteins. We computationally examined the interaction of these with SARS-CoV-2 proteins and, in the case of VKORC1, we describe its binding to ORF7a in detail. We examined the occurrence of variants of each of these proteins across populations and interrogated their potential contribution to COVID-19 severity. Potential mechanisms, by which some of these variants may contribute to disease, are proposed. Some of these variants are prevalent in minority groups that are disproportionally affected by severe COVID-19. Therefore, we are proposing that further investigation around these variants may lead to better understanding of disease pathogenesis in minority groups and more informed therapeutic approaches.


Assuntos
Coagulação Sanguínea , Proteínas Sanguíneas/genética , Proteína Inibidora do Complemento C1/genética , Proteínas de Ligação a Poli(A)/genética , Vitamina K Epóxido Redutases/genética , Anticoagulantes/administração & dosagem , Proteínas Sanguíneas/metabolismo , /virologia , Proteína Inibidora do Complemento C1/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Modelos Moleculares , Mutação , Proteínas de Ligação a Poli(A)/metabolismo , Ligação Proteica , Índice de Gravidade de Doença , Proteínas Virais/metabolismo , Vitamina K Epóxido Redutases/metabolismo , Varfarina/administração & dosagem
4.
Medicine (Baltimore) ; 100(7): e24695, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607810

RESUMO

RATIONALE: Cisplatin is one of the key drugs that is frequently used for treating various types of malignancies. Although renal and digestive toxicities are well-known cisplatin-related toxicities, attention should also be paid to acute aortic thrombosis, a relatively rare but potentially fatal disorder caused by cisplatin. Additionally, D-dimer is mainly measured to detect venous thromboembolism or disseminated intravascular coagulation, whereas its usefulness for detecting aortic thrombosis remains unclear. Here, we report a case of squamous cell lung cancer treated with cisplatin-based chemotherapy, wherein acute aortic thrombosis was diagnosed based on elevated D-dimer levels. PATIENT CONCERNS: A 65-year-old man with stage IV squamous cell lung cancer presented with elevated D-dimer levels during treatment with second-line chemotherapy with cisplatin and S-1. Contrast-enhanced computed tomography (CT) revealed an intramural thrombus, which had not been previously identified, extending from the abdominal aorta to the common iliac artery. DIAGNOSES: We diagnosed the patient as having acute aortic thrombosis caused by cisplatin. INTERVENTIONS: The patient received intravenous administration of unfractionated heparin for 9 days followed by oral warfarin. OUTCOMES: One month after initiating treatment, the patient's D-dimer levels decreased to the normal range, and contrast-enhanced CT revealed that the thrombi had nearly completely disappeared without any sequelae or organ damage. LESSONS: Our findings revealed that cisplatin can cause acute aortic thrombosis and that regular measurements of D-dimer levels before and during chemotherapy may contribute to the early detection of acute aortic thrombosis.


Assuntos
Doenças da Aorta/patologia , Cisplatino/toxicidade , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose/induzido quimicamente , Administração Intravenosa , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Antineoplásicos/toxicidade , Carcinoma de Células Escamosas/tratamento farmacológico , Produtos de Degradação da Fibrina e do Fibrinogênio/efeitos dos fármacos , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias/métodos , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/uso terapêutico
5.
Am J Cardiol ; 146: 22-28, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33529622

RESUMO

There are limited data regarding direct oral anticoagulants (DOACs) for stroke prevention in patients with bioprosthetic heart valves (BHVs) and atrial fibrillation (AF). The objectives of this study were to evaluate the ambulatory utilization of DOACs and to compare the effectiveness and safety of DOACs versus warfarin in patients with AF and BHVs. We conducted a retrospective cohort study at a large integrated health care delivery system in California. Patients with BHVs and AF treated with warfarin, dabigatran, rivaroxaban, or apixaban between September 12, 2011 and June 18, 2020 were identified. Inverse probability of treatment-weighted comparative effectiveness and safety of DOACs compared with warfarin were determined. Use of DOACs gradually increased since 2011, with a significant upward in trend after a stay-at-home order related to COVID-19. Among 2,672 adults with BHVs and AF who met the inclusion criteria, 439 were exposed to a DOAC and 2233 were exposed to warfarin. For the primary effectiveness outcome of ischemic stroke, systemic embolism and transient ischemic attack, no significant association was observed between use of DOACs compared with warfarin (HR 1.19, 95% CI 0.96 to 1.48, p = 0.11). Use of DOACs was associated with lower risk of the primary safety outcome of intracranial hemorrhage, gastrointestinal bleeding, and other bleed (HR 0.69, 95% CI 0.56 to 0.85, p < 0.001). Results were consistent across multiple subgroups in the sensitivity analyses. These findings support the use of DOACs for AF in patients with BHVs.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Bioprótese , Doenças das Valvas Cardíacas/complicações , Valvas Cardíacas , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Fibrilação Atrial/complicações , Feminino , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Adulto Jovem
7.
Hematology ; 25(1): 489-493, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33317427

RESUMO

BACKGROUND: Four-factor prothrombin complex concentrate (4F-PCC) is widely used for urgent reversal of anticoagulation with warfarin, but the optimal 4F-PCC dosing approach is unknown. Herein, we sought to determine the efficacy of a novel fixed, weight-based dosing nomogram. METHODS: We retrospectively studied consecutive adult patients receiving fixed, weight-based 4F-PCC dosing for warfarin reversal between 30 April 2009 and 31 December 2010. The primary outcome was reversal of warfarin anticoagulation, defined as INR ≤1.5 within 6 h. Secondary outcome was the occurrence of thromboembolic events. RESULTS: A total of 227 patients (56% male), with a median age of 74 years and a median weight of 76kg were evaluated. The most common indications for 4F-PCC were active bleeding (37.4%: 12.7% intracranial, 12.3% gastrointestinal, 4.0% trauma, 8.4% other), reversal for a procedure (22.0%), reversal for surgery (29.5%) or other (11.1%). 66.1% of patients achieved an INR ≤1.5 within 6 h of 4F-PCC administration. 95.0% (57/60) of patients completed a planned procedure and 95.7% (67/70) of patients completed a planned surgery. The median baseline INR was 2.9 (1.5-10) and decreased significantly to a median of 1.3 (1.0-3.7) (p < .001) post-4F-PCC administration. There was no statistically significant difference in response to a fixed, weight-based dose of 4F-PCC based on pre-PCC INR, as long as the pre-treatment INR was ≤ 4.5. Although the majority of patients in our study (99%) received doses over 1000IU, rates of thrombosis were low (1.8%). CONCLUSION: Fixed, weight-based dosing of 4F-PCC is effective for reversing warfarin anticoagulation in patients with a pre-dosing INR ≤ 4.5.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Fatores de Coagulação Sanguínea/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Varfarina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Varfarina/administração & dosagem
9.
Am Surg ; 86(9): 1062-1066, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33049165

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) have overtaken warfarin as the preferred anticoagulants for stroke prevention with atrial fibrillation and for treatment of venous thromboembolism. Despite the increased prevalence of DOACs, literature studying their impact on trauma patients with intracranial hemorrhage (ICH) remains limited. Most DOAC reversal agents have only been recently available, and concerns for worse outcomes with DOACs among this population remain. This study aims to assess the outcomes of patients with traumatic ICH taking DOACs compared with those taking warfarin. METHODS: A retrospective analysis of patients with traumatic ICH over a 5-year period was conducted. Demographics, injury severity, medication, and outcome data were collected for each patient. Patients taking warfarin and DOACs were compared. RESULTS: 736 patients had traumatic ICH over the study period, 75 of which were on either DOACs (25 patients) or warfarin (50 patients). The median age of the anticoagulated patients was 78 years; 52% were female, and 91% presented secondary to a fall. DOACs were reversed at close to half the rate of warfarin (40% vs 77%; P = .032). Despite this, the 2 groups had similar rates of worsening examination, need for operative intervention, and in-hospital mortality. In the follow-up, fewer patients taking DOACs had died at 6-months postinjury compared with those taking warfarin (8% vs 30%; P = .041). DISCUSSION: Despite DOACs being reversed at nearly half the rate of warfarin, patients presenting with traumatic ICH on warfarin had higher 6-month mortality suggesting a potential survival advantage for DOACs over warfarin in this population.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Hemorragia Intracraniana Traumática/complicações , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Coagulação Sanguínea/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hemorragia Intracraniana Traumática/sangue , Hemorragia Intracraniana Traumática/mortalidade , Masculino , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
10.
J Med Case Rep ; 14(1): 188, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054805

RESUMO

BACKGROUND: Currently, there is minimal data available highlighting the prevalence of venous thromboembolism in patients infected with coronavirus disease 2019 (COVID-19). This case report with a literature review emphasizes a unique presentation of COVID-19 that is highly important for health care providers to consider when treating their patients. CASE REPORT: A 65-year-old Caucasian male patient presented to the emergency department with a 2-day history of dyspnea on exertion after his wife's recent diagnosis of COVID-19. He additionally had experienced a couple of episodes of self-resolving diarrhea a few days before presentation. Based on the patient's clinical presentation and the laboratory workup identifying an elevated D-dimer, a computed tomography angiogram of the chest was obtained, which was significant for moderately large, bilateral pulmonary emboli with a saddle embolus, and an associated small, left lower lobe, pulmonary infarct. Ultrasound of the lower extremity showed non-occlusive deep vein thrombosis at the distal left femoral vein to the left popliteal vein. The patient was additionally diagnosed with COVID-19 when the results of the COVID-19 polymerase chain reaction test returned as positive. The patient was admitted to the COVID unit, and he was started on an intravenously administered, unfractionated heparin drip for management of his bilateral pulmonary emboli and deep vein thrombosis. The patient's clinical condition improved significantly with anticoagulation, and he was observed in the hospital for 3 days, after which he was discharged home on the enoxaparin bridge with warfarin. Post-discharge telephone calls at day 10 and week 4 revealed that the patient was appropriately responding to anticoagulation treatment and had no recurrence of his symptoms related to venous thromboembolism and COVID-19. CONCLUSION: As COVID-19 continues to lead to significant mortality, more data is emerging that is exposing its perplexing pathogenicity. Meanwhile, the presentation of venous thromboembolism in patients with COVID-19 remains an unusual finding. It is imperative for health care providers to be mindful of this unique association to make necessary diagnostic evaluations and provide appropriate treatment for the patients.


Assuntos
Infecções por Coronavirus , Enoxaparina/administração & dosagem , Veia Femoral/diagnóstico por imagem , Heparina/administração & dosagem , Pandemias , Pneumonia Viral , Embolia Pulmonar , Tromboembolia Venosa , Varfarina/administração & dosagem , Idoso , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Embolia Pulmonar/terapia , Resultado do Tratamento , Ultrassonografia/métodos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/terapia
11.
Medicine (Baltimore) ; 99(36): e22054, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899067

RESUMO

BACKGROUND: Anticoagulant therapy is used for stroke prevention and proved to be effective and safe in the long term. The study aims to analyse the cost-effectiveness relationship of using of direct-acting oral anticoagulants vs vitamin K antagonists to prevent ischaemic stroke in patients with nonvalvular atrial fibrillation, including all the active ingredients marketed in Spain, prescribed for 2 years in the Primary Care service of the Institut Català de la Salut. METHODS: Population-based cohort study, in which the cost of the 2 treatment groups will be evaluated. Direct costs (pharmacy, primary care, emergency and hospitalization) and indirect costs (lost productivity) will be included from a social perspective. Effectiveness (assessed as the occurrence of a health event, the 1 of primary interest being stroke) will be determined, with a 2-year time horizon and a 3% discount rate. The average cost of the 2 groups of drugs will be compared using a regression model to determine the factors with the greatest influence on determining costs. We will carry out a univariate ('one-way') deterministic sensitivity analysis. DISCUSSION: We hope to provide relevant information about direct and indirect costs of oral anticoagulants, which, together with aspects of effectiveness and safety, could help shape the consensual decision-making of evaluating bodies.


Assuntos
Acenocumarol/economia , Anticoagulantes/economia , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/patologia , Ensaios Clínicos Pragmáticos como Assunto/métodos , Varfarina/economia , Acenocumarol/administração & dosagem , Acenocumarol/uso terapêutico , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/prevenção & controle , Análise Custo-Benefício , Inibidores do Fator Xa , Humanos , Atenção Primária à Saúde/organização & administração , Segurança , Espanha/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Varfarina/uso terapêutico
13.
J Stroke Cerebrovasc Dis ; 29(9): 105025, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807440

RESUMO

PURPOSE: There are various patterns in determining the choice of the first-line antithrombotic agent for acute stroke with non-valvular atrial fibrillation. We investigated the efficacy and safety of non-vitamin K oral anticoagulants as first-line antithrombotics for patients with acute stroke and non-valvular atrial fibrillation. MATERIALS AND METHODS: Patients with non-valvular atrial fibrillation and ischemic stroke or transient ischemic attack within 24 h from stroke onset were included. On the basis of the first regimen used and the regimen within 7 days after admission, the study population was divided into three groups: 1) antiplatelet switched to warfarin (A-W), 2) antiplatelet switched to NOAC (A-N), and 3) NOAC only (N only). We compared the occurrence of early neurologic deterioration, symptomatic intracranial hemorrhage, systemic bleeding, and poor functional outcome at 90 days. RESULTS: Of 314 included patients, 164, 53, and 97 were classified into the A-W, A-N, and N only groups, respectively. Early neurologic deterioration was most frequently observed in the A-W group (9.1%), followed by the A-N (5.7%) and N only (1.0%) groups (p = 0.017). Multivariable analysis adjusting for potential confounders demonstrated that the N only group was independently associated with a lower rate of early neurologic deterioration (odds ratio [OR] 0.104, 95% CI 0.013-0.831) or poor functional outcome at 90 days (OR 0.450, 95% CI 0.215-0.940) than the A-W group. However, the rate of symptomatic intracranial hemorrhage or any systemic bleeding event did not differ among the groups. CONCLUSION: Using non-vitamin K oral anticoagulants as the first-line regimen for acute ischemic stroke may help prevent early neurologic deterioration without increasing the bleeding risk.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Substituição de Medicamentos , Inibidores da Agregação de Plaquetas/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Varfarina/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Avaliação da Deficiência , Substituição de Medicamentos/efeitos adversos , Feminino , Humanos , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Recuperação de Função Fisiológica , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Varfarina/efeitos adversos
14.
BMJ Case Rep ; 13(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747597

RESUMO

We describe a patient with COVID-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. A 58-year-old man, without major comorbidity, was admitted with a 14-day history of breathlessness. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was confirmed by laboratory testing. Initial imaging revealed COVID-19 pneumonia but no pulmonary thromboembolism (PTE) on CT pulmonary angiography (CTPA). The patient subsequently developed respiratory failure and left foot ischaemia associated with a rising D-dimer. Repeat CTPA and lower limb CT angiography revealed simultaneous bilateral PTE, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. This case highlights a broad range of vascular sequalae associated with COVID-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation.


Assuntos
Infecções por Coronavirus , Enoxaparina/administração & dosagem , Cardiopatias , Pandemias , Doença Arterial Periférica , Pneumonia Viral , Embolia Pulmonar , Trombose , Varfarina/administração & dosagem , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Deterioração Clínica , Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Cardiopatias/terapia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/terapia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Embolia Pulmonar/terapia , Trombose/diagnóstico , Trombose/etiologia , Trombose/terapia , Resultado do Tratamento
15.
Stroke ; 51(8): 2355-2363, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640939

RESUMO

BACKGROUND AND PURPOSE: As a result of contraindications (eg, frailty, cognitive impairment, comorbidities) or patient refusal, many patients with stroke and atrial fibrillation cannot be discharged on oral anticoagulant. Among them, the proportion of potential candidates for left atrial appendage closure (LAAC) and their 12-month outcome is not well known. METHODS: The prospective WATCH-AF registry (Warfarin Aspirin Ten-A Inhibitors and Cerebral Infarction and Hemorrhage and Atrial Fibrillation) enrolled consecutive patients admitted within 72 hours of an acute stroke associated with atrial fibrillation in 2 stroke centers. Scales to evaluate stroke severity, disability, functional independence, risk of fall, cognition, ischemic and hemorrhagic risk-stratification, and comorbidities were systematically collected at admission, discharge, 3, 12 months poststroke. The 2 main end points were death or dependency (modified Rankin Scale score >3) and recurrent stroke (brain infarction and brain hemorrhage). RESULTS: Among 400 enrolled patients (370 with brain infarction, 30 with brain hemorrhage), 31 died before discharge and 57 (14.3%) were possible European Heart Rhythm Association/European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Rhythm Society candidates for LAAC. At 12 months, the rate of death or dependency was 17.9%, and the rate of stroke recurrence was 9.8% in the 274/400 (68.5%) patients discharged on a long-term oral anticoagulant strategy, as compared with 17.5% and 24.7%, respectively, in 57 patients candidate for LAAC. As compared with patients on a long-term oral anticoagulant strategy, there was a 2-fold increase in the risk of stroke recurrence in the group with an indication for LAAC (adjusted hazard ratio, 2.58 [95% CI, 1.40-4.76]; P=0.002). CONCLUSIONS: Fourteen percent of patients with stroke associated with atrial fibrillation were potential candidates for LAAC. The 12-month stroke risk of these candidates was 3-fold the risk of anticoagulated patients.


Assuntos
Anticoagulantes/administração & dosagem , Apêndice Atrial , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Sistema de Registros , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Prevalência , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento , Varfarina/administração & dosagem
16.
Stroke ; 51(8): 2364-2373, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640949

RESUMO

BACKGROUND AND PURPOSE: The comparative effectiveness of direct-acting oral anticoagulants, compared with warfarin, for risks of stroke/systemic embolism, major bleeding, or death have not been studied in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease. METHODS: Medicare data from 2011 to 2017 were used to identify patients with stages 3, 4, or 5 chronic kidney disease and new atrial fibrillation who received a new prescription for warfarin, apixaban, rivaroxaban, or dabigatran. We estimated marginal hazard ratios with 95% CIs for the association of each direct-acting oral anticoagulant, compared with warfarin, for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses. RESULTS: A total of 22 739 individuals met criteria (46.3% warfarin, 29.6% apixaban, 17.2% rivaroxaban, 6.9% dabigatran). Across the groups of anticoagulant users, mean age was 78.4 to 79.0 years; 50.3% to 51.4% were women, and 80.3% to 82.8% had stage 3 chronic kidney disease. In the as-treated analysis, for stroke/systemic embolism, hazard ratios, all compared with warfarin, were 0.70 (0.51-0.96) for apixaban, 0.80 (0.54-1.17) for rivaroxaban, and 1.15 (0.69-1.94) for dabigatran. For major bleeding, analogous hazard ratios were 0.47 (0.37-0.59) for apixaban, 1.05 (0.85-1.30) for rivaroxaban, and 0.95 (0.70-1.31) for dabigatran. There was no difference in the risk of all-cause mortality between the direct-acting oral anticoagulants and warfarin. Results of the intention-to-treat analysis were similar. CONCLUSIONS: Apixaban, compared with warfarin, was associated with decreased risk of stroke/systemic embolism and major bleeding; risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Medicare , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Varfarina/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Medicare/tendências , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Estados Unidos/epidemiologia , Varfarina/efeitos adversos , Adulto Jovem
18.
Clin Drug Investig ; 40(9): 839-845, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32607688

RESUMO

BACKGROUND AND OBJECTIVE: Current guidelines recommend anticoagulation with a vitamin K antagonist (warfarin) after a bioprosthetic valve replacement. There is minimal literature evaluating direct oral anticoagulants (DOACs) in patients who have just received a bioprosthetic aortic valve replacement (AVR) or mitral valve replacement (MVR). The purpose of this study was to investigate any differences in efficacy and safety for patients taking a DOAC, compared with warfarin, after a bioprosthetic AVR or MVR. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in patients who received bioprosthetic valve replacements at a large teaching hospital from 2014 to 2018. Patients included in this study received either warfarin or a DOAC following bioprosthetic AVR or MVR, and were maintained on the same agent throughout the 6-month follow-up period. The primary efficacy outcome was the incidence of thromboembolic complications and the primary safety outcome was the incidence of major bleeding within 6 months following surgery. The rate of readmission was assessed as a secondary endpoint. RESULTS: A total of 197 patients were included; 70 patients received warfarin and 127 patients received a DOAC (apixaban, n = 86; rivaroxaban, n = 40; dabigatran, n = 1). Three patients experienced thromboembolic events, all of which occurred in the DOAC group (0% vs. 2.4%; p = 0.20). Major bleeding occurred in 11 patients-two in the warfarin group and nine in the DOAC group (2.9% vs. 7.1%; p = 0.22). Sixty-one patients were readmitted within the 6-month time frame, with 26 readmissions in the warfarin group and 35 readmissions in the DOAC group (37% vs. 27%; p = 0.16). CONCLUSIONS: This small, exploratory study found similar rates of thromboembolic complications and major bleeding events in patients who received a DOAC versus warfarin after a recent bioprosthetic AVR or MVR. This study was limited by its retrospective nature and its sample size. Larger, randomized controlled trials are needed to further determine the efficacy and safety of DOACs in this patient population.


Assuntos
Anticoagulantes/uso terapêutico , Bioprótese , Dabigatrana/uso terapêutico , Próteses Valvulares Cardíacas , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Tromboembolia/induzido quimicamente , Varfarina/administração & dosagem , Varfarina/efeitos adversos
19.
Yakugaku Zasshi ; 140(10): 1269-1274, 2020 Oct 01.
Artigo em Japonês | MEDLINE | ID: mdl-32684555

RESUMO

We previously reported that tolvaptan may influence warfarin pharmacodynamics in vivo; however, the mechanism responsible for this influence was not clear. In this study, we investigated the drug-drug interactions between warfarin and tolvaptan by measuring warfarin blood concentrations in 18 patients who received warfarin therapy and in 24 who received warfarin+tolvaptan therapy. The free warfarin concentrations significantly increased in patients who were also receiving oral tolvaptan (p=0.04). In vitro albumin-binding experiments showed that the free warfarin concentrations significantly increased with the addition of tolvaptan, in a dose-dependent manner, through albumin-binding substitution (approximately 2.5 times). Both clinical and in vitro data showed that tolvaptan increased the unbound warfarin serum concentration. The prothrombin time-international normalized ratio (PT-INR) tended to increase within 2 weeks when tolvaptan was added at clinically used doses (p=0.14). Special attention is warranted in cases with a serum tolvaptan concentration of ≥125 ng/mL (≥7.5 mg/d) for at least 2 weeks following oral tolvaptan administration.


Assuntos
Anticoagulantes/sangue , Interações Medicamentosas , Coeficiente Internacional Normatizado , Tempo de Protrombina , Tolvaptan/farmacologia , Varfarina/sangue , Varfarina/farmacologia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Albuminas/metabolismo , Anticoagulantes/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Fatores de Tempo , Tolvaptan/administração & dosagem , Varfarina/administração & dosagem , Varfarina/metabolismo
20.
PLoS Med ; 17(7): e1003146, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32673305

RESUMO

BACKGROUND: Atrial fibrillation (AF) is underdiagnosed and especially undertreated in China. We aimed to investigate the prevalence of unknown and untreated AF in community residents (≥65 years old) and to determine whether an education intervention could improve oral anticoagulant (OAC) prescription. METHODS AND FINDINGS: We performed a single-time point screening for AF with a handheld single-lead electrocardiography (ECG) in Chinese residents (≥65 years old) in 5 community health centers in Shanghai from April to September 2017. Disease education and advice on referral to specialist clinics for OAC treatment were provided to all patients with actionable AF (newly detected or undertreated known AF) at the time of screening, and education was reinforced at 1 month. Follow-up occurred at 12 months. In total, 4,531 participants were screened (response rate 94.7%, mean age 71.6 ± 6.3 years, 44% male). Overall AF prevalence was 4.0% (known AF 3.5% [n = 161], new AF 0.5% [n = 22]). The 183 patients with AF were older (p < 0.001), taller (p = 0.02), and more likely to be male (p = 0.01), and they had a higher prevalence of cardiovascular disease than those without AF (p < 0.001). In total, 85% (155/183) of patients were recommended for OAC treatment by the established guidelines (CHA2DS2-VASc ≥ 2 for men; ≥ 3 for women). OAC prescription rate for known AF was 20% (28/138), and actionable AF constituted 2.8% of all those screened. At the 12-month follow-up in 103 patients (81% complete), despite disease education and advice on specialist referral, only 17 attended specialist clinics, and 4 were prescribed OAC. Of those not attending specialist clinics, 71 chose instead to attend community health centers or secondary hospital clinics, with none prescribed OAC, and 15 had no review. Of the 17 patients with new AF and a class 1 recommendation for OAC, only 3 attended a specialist clinic, and none were prescribed OAC. Of the 28 AF patients taking OAC at baseline, OAC was no longer taken in 4. Ischemic stroke (n = 2) or death (n = 3) occurred in 5/126 (4%), with none receiving OAC. As screening was performed at a single time point, some paroxysmal AF cases may have been missed; thus, the rate of new AF may be underestimated. CONCLUSIONS: We demonstrated a noticeable gap in AF detection and treatment in community-based elderly Chinese: actionable AF constituted a high proportion of those screened. Disease education and advice on specialist referral are insufficient to close the gap. Before more frequent or intensive screening for unknown AF could be recommended in China, greater efforts must be made to increase appropriate OAC therapy in known AF to prevent AF-related stroke.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Fibrilação Atrial/epidemiologia , China/epidemiologia , Centros Comunitários de Saúde , Estudos Transversais , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Programas de Rastreamento , Prevalência , Estudos Prospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Varfarina/administração & dosagem , Varfarina/uso terapêutico
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