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1.
Medicine (Baltimore) ; 99(45): e23031, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157953

RESUMO

RATIONALE: The evidence for outpatient pulmonary embolism (PE) management apart from hospitalization is expanding. The availability and ease of direct oral anticoagulants have facilitated this transition. The literature, however, is sparse on the topic of comprehensive management of pulmonary embolism in the primary care clinic setting. As such, the role of the primary care physician in the complete diagnosis, risk stratification for outpatient eligibility, and initiation of treatment is unclear. CASE PRESENTATIONS: Case 1: A 33-year-old man with known heterozygous Factor V Leiden mutation and a remote history of deep vein thrombosis presented to his primary care physician's office with 2 days of mild pleuritic chest pain and a dry cough after a recent transcontinental flight. Case 2: A 48-year-old man with a complex medical history including recent transverse myelitis presented to his primary care family physician with dyspnea and pleuritic chest pain for 6 days. DIAGNOSIS: Case 1: Computed tomographic pulmonary angiography that same afternoon showed multiple bilateral segmental and subsegmental emboli as well as several small pulmonary infarcts. Case 2: The patient's D-dimer was elevated at 1148 ng/mL. His physician ordered a computed tomographic pulmonary angiography, performed that evening, which showed segmental and subsegmental PE. INTERVENTIONS: Both patients were contacted by their respective physicians shortly after their diagnoses and, in shared decision-making, opted for treatment at home with 5 days of enoxaparin followed by dabigatran. OUTCOMES: Neither patient developed recurrence nor complications in the subsequent 3 months. LESSONS: These cases, stratified as low risk using the American College of Chest Physicians criteria and the PE Severity Index, are among the first in the literature to illustrate comprehensive primary care-based outpatient PE management. Care was provided within an integrated delivery system with ready, timely access to laboratory, advanced radiology, and allied health services. This report sets the stage for investigating the public health implications of comprehensive primary care-based PE management, including cost-savings as well as enhanced patient follow-up and patient satisfaction.


Assuntos
Dor no Peito/etiologia , Dispneia/etiologia , Transferência de Pacientes/métodos , Médicos de Atenção Primária/normas , Embolia Pulmonar/tratamento farmacológico , Doença Aguda , Adulto , Assistência Ambulatorial , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Dor no Peito/diagnóstico , Angiografia por Tomografia Computadorizada/métodos , Dabigatrana/uso terapêutico , Tomada de Decisão Compartilhada , Dispneia/diagnóstico , Enoxaparina/uso terapêutico , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Mielite Transversa/complicações , Mielite Transversa/diagnóstico , Transferência de Pacientes/estatística & dados numéricos , Médicos de Atenção Primária/estatística & dados numéricos , Embolia Pulmonar/diagnóstico por imagem , Medição de Risco , Resultado do Tratamento , Trombose Venosa/complicações , Trombose Venosa/diagnóstico
2.
Lancet ; 396(10264): 1767-1776, 2020 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-33248499

RESUMO

Currently licenced direct oral anticoagulants selectively target thrombin (eg, dabigatran) or coagulation factor Xa (eg, apixaban, betrixaban, edoxaban, and rivaroxaban). Designed to be given in fixed doses without routine monitoring, direct oral anticoagulants have a lower propensity for food and drug interactions than do vitamin K antagonists, and in randomised controlled trials involving around 250 000 patients, they were at least as effective for prevention and treatment of thrombosis and were associated with a lower risk of life-threatening bleeding. The absolute benefits of direct oral anticoagulants over vitamin K antagonists are modest; however, guidelines recommend them in preference to vitamin K antagonists for most indications because of their ease of use and superior safety. The greatest benefits of direct oral anticoagulants are likely to be in patients who were previously deemed unsuitable for vitamin K antagonist therapy. The emergence of generic preparations is expected to further increase the uptake of direct oral anticoagulants, particularly in countries where they are currently not widely used because of cost. Direct oral anticoagulants are contraindicated in patients with mechanical heart valves and should be used with caution or avoided in patients with advanced kidney or liver disease. In this Therapeutics paper, we review the pharmacology of direct oral anticoagulants, summarise the evidence that led to their approval and incorporation into treatment guidelines, and explore key unresolved issues. We also briefly discuss future perspectives for the development of oral anticoagulants.


Assuntos
Anticoagulantes , Dabigatrana , Inibidores do Fator Xa , Pirazóis , Piridinas , Piridonas , Rivaroxabana , Tiazóis , Administração Oral , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/farmacologia , Inibidores do Fator Xa/uso terapêutico , Hemorragia/complicações , Humanos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Piridonas/farmacologia , Piridonas/uso terapêutico , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Tromboembolia Venosa/prevenção & controle
3.
Kardiologiia ; 60(9): 102-109, 2020 Oct 14.
Artigo em Russo | MEDLINE | ID: mdl-33131481

RESUMO

Aim To compare efficacy and safety of direct oral anticoagulants (DOACs) for prevention of stroke in patients with nonvalvular atrial fibrillation and reduced creatinine clearance.Material and methods Systematic search for literature and indirect comparison of DOACs were performed.Results The indirect comparison included five randomized clinical trials. The DOACs were comparable by the efficacy of preventing stroke and systemic embolism. The safety profiles had differences. Apixaban significantly decreased the relative risk of major bleeding compared to rivaroxaban by 27 % (relative risk (RR) 0.73; 95 % confidence interval (CI): 0.55-0.98). The apixaban advantage was even greater in the group of patients with a creatinine clearance <50 ml/min: RR was reduced by 48 % compared to rivaroxaban (RR=0.52; 95 % CI: 0.32-0.84), by 50 % compared to dabigatran 300 mg/day (RR=0.50; 95 % CI: 0.31-0.81), and by 48 % compared to dabigatran 220 mg/day (RR=0.52; 95 % CI: 0.32-0.85)Conclusion The indirect comparison of DOACs showed that their efficacy was comparable. With respect of safety, apixaban is the preferrable DOAC for patients with atrial fibrillation and creatinine clearance below 50 ml/min.


Assuntos
Fibrilação Atrial , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Humanos , Piridonas/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
4.
J Stroke Cerebrovasc Dis ; 29(11): 105250, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066907

RESUMO

The plasminogen activator inhibitor-1 (PAI-1) 4G/4G homozygous genotype represents a genetic thrombophilia that has been associated with enhanced risk of arterial and venous thrombotic events. The optimal anticoagulation strategy for PAI-1 4G homozygous patients is unclear. Herein we present a case of a patient with PAI-1 4G/4G homozygosity who was placed on dabigatran after developing cerebral venous sinus thrombosis (CVST), but who then suffered an acute myocardial infarction several weeks later. We seek to highlight the relationship between the PAI-1 4G/4G genotype and risk of CVST, as well as discuss our management strategy in the aftermath of dabigatran failure.


Assuntos
Hemostasia/genética , Homozigoto , Infarto do Miocárdio/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Trombose dos Seios Intracranianos/genética , Adulto , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Dabigatrana/uso terapêutico , Substituição de Medicamentos , Predisposição Genética para Doença , Hemostasia/efeitos dos fármacos , Heparina/uso terapêutico , Humanos , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Fenótipo , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico , Fatores de Tempo , Falha de Tratamento , Varfarina/uso terapêutico
5.
Medicine (Baltimore) ; 99(35): e21922, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871929

RESUMO

RATIONALE: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype may include the antiplatelet agents, anticoagulants, or endovascular intervention. PATIENT CONCERNS: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F, fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made. DIAGNOSES: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke. INTERVENTIONS: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the thrombus. Dabigatran (110 mg bid) started on day 7. OUTCOMES: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent speech in mild extent. LESSONS: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of ischemic stroke among patients with cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antitrombinas/uso terapêutico , Trombose das Artérias Carótidas/terapia , Artéria Carótida Interna , Infarto da Artéria Cerebral Média/induzido quimicamente , Terapia Trombolítica , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Administração Oral , Trombose das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Dabigatrana/uso terapêutico , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/terapia , Neoplasias do Colo Sigmoide/complicações , Neoplasias do Colo Sigmoide/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico
6.
Eur Heart J ; 41(41): 4037-4046, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32984892

RESUMO

AIMS: The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability. METHODS AND RESULTS: Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level. CONCLUSIONS: Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.


Assuntos
Fibrilação Atrial/sangue , Betacoronavirus , Infecções por Coronavirus/sangue , Peptidil Dipeptidase A/sangue , Pneumonia Viral/sangue , Idoso , Antitrombinas/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Biomarcadores/sangue , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Dabigatrana/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico
7.
Clin Drug Investig ; 40(11): 1053-1061, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32886321

RESUMO

BACKGROUND AND OBJECTIVES: The results of randomised clinical trials (RCTs) on direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) can mostly be applied to primary prevention in relatively young patients, since only a minority of patients included in these trials were receiving DOACs for secondary prevention. The real-life secondary prevention subgroup, comprising mostly elderly and high-risk patients, remains a point of interest where further exploration is needed. Our objective was to explore the effectiveness and safety of DOACs for secondary prevention in the real-life conditions. METHODS: In a six-year (2012-2018) period all consecutive patients with a history of transient ischaemic attack (TIA) or stroke, recorded NVAF and prescription of DOAC, were included in this single-centre registry. Choice of the DOAC and dose was based on the discretion of the attending clinician. Data regarding recurrent stroke/TIA or other embolic events, intracranial haemorrhage, other major bleeding, adherence and potential changes of therapy were collected and analysed. RESULTS: During the study period, 566 patients were prescribed a DOAC for secondary stroke prevention, and follow-up data were available for 510 patients, with an average observational time of 2.6 years. The mean age of patients was 77.9 ± 8.7 years. The mean CHA2DS2-VASc and HAS-BLED scores were 5.1 ± 1.2 and 2.4 ± 0.6, respectively. Dabigatran was prescribed in 66%, apixaban in 21% and rivaroxaban in 13% of patients; 58% of patients were prescribed the reduced dose of DOAC. The overall yearly incidence of recurrent stroke, major bleeding and intracranial bleeding was 1.7%, 1.6% and 0.2%, respectively. Thus, we found similar effectiveness and safety of both standard and reduced dose of DOACs for secondary stroke prevention, compared to the RCT and large registries. CONCLUSIONS: Our real-life data study suggests that secondary stroke prevention with DOACs is as effective and safe as primary prevention, both in standard and reduced doses, in a typical group of patients who are older than patients included in RCTs.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Dabigatrana/uso terapêutico , Embolia/prevenção & controle , Feminino , Humanos , Incidência , Ataque Isquêmico Transitório/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Sistema de Registros , Rivaroxabana/uso terapêutico , Prevenção Secundária
8.
Yakugaku Zasshi ; 140(12): 1477-1483, 2020 Dec 01.
Artigo em Japonês | MEDLINE | ID: mdl-32921648

RESUMO

Asthma and chronic obstructive pulmonary disease (COPD) are characterised by chronic inflammation in the lung that is associated with airway obstruction. Inhaled therapy with a combination of corticosteroid and a long-acting ß2-agonist is an effective anti-inflammatory medicine for asthma, but in patients with severe asthma and COPD fails to completely control these symptoms with current therapies. The inflammatory process in these diseases, which involves activation of the coagulation and fibrinolytic system in the lung, offers the opportunity for alternative anti-inflammatory therapies. In this study, we investigated the effects of anti-coagulants on lipopolysaccharide (LPS)-induced airway inflammation in mice. A/J mice were exposed to LPS, a bacterial endotoxin, intranasally and accumulation of inflammatory cells, TNF-α, C-X-C motif chemokine (CXCL) 1, and osteopontin in bronchoalveolar lavage fluid (BALF) was monitored by flow cytometry and an enzyme-linked immunosorbent assay. LPS exposure induced airway neutrophilia and accumulation of TNF-α, CXCL1, and osteopontin in BALF. This LPS-induced airway inflammation was not relieved using a corticosteroid, fluticasone propionate (FP), or a direct inhibitor of Factor Xa, rivaroxaban. In contrast, a direct thrombin inhibitor, dabigatran, inhibited LPS-induced airway neutrophilia and decreased inflammatory cytokine production in a dose dependent manner. Furthermore, combination of dabigatran and FP elicited stronger inhibition of LPS-induced airway inflammation. Therefore, these results suggest that dabigatran could be an effective new therapy for severe respiratory diseases.


Assuntos
Antitrombinas/uso terapêutico , Asma/tratamento farmacológico , Dabigatrana/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Antitrombinas/farmacologia , Asma/induzido quimicamente , Asma/diagnóstico , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Quimiocina CXCL1/análise , Dabigatrana/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Fluticasona/uso terapêutico , Inflamação , Mediadores da Inflamação/análise , Masculino , Camundongos Endogâmicos , Osteopontina/análise , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fator de Necrose Tumoral alfa/análise
9.
Medicine (Baltimore) ; 99(27): e21025, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629725

RESUMO

BACKGROUND: Given the huge burden of atrial fibrillation (AF) and AF-related stroke in Asia, stroke prevention represents an urgent issue in this region. We herein performed a network meta-analysis to examine the role of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with AF. METHODS: A systematic search of the publications was conducted in PubMed and Embase databases for eligible studies until July 2019. The odds ratios (ORs) and 95% confidence intervals (CIs) were regarded as the effect estimates. The surface under the cumulative ranking area (SUCRA) for the ranking probabilities was calculated. RESULTS: A total of 17 studies were included. For comparisons of NOACs vs warfarin, dabigatran (OR = 0.77, 95% CI 0.68-0.86), rivaroxaban (OR = 0.72, 95% CI 0.65-0.81), apixaban (OR = 0.56, 95% CI 0.49-0.65), but not edoxaban reduced the risk of stroke or systemic embolism, wheres dabigatran (OR = 0.56, 95% CI 0.41-0.76), rivaroxaban (OR = 0.66, 95% CI 0.50-0.86), apixaban (OR = 0.49, 95% CI 0.36-0.66), and edoxaban (OR = 0.34, 95% CI 0.24-0.49) decreased the risk of major bleeding. In reducing the risk of stroke or systemic embolism, apixaban and rivaroxaban ranked the best and second best (SUCRA 0.2% and 31.4%, respectively), followed by dabigatran (50.2%), edoxaban (75.2%), and warfarin (93.0%). In reducing the risk of major bleeding, edoxaban, and apixaban ranked the best and second best (1.5% and 30.8%, respectively), followed by dabigatran (48.4%), rivaroxaban (69.2%), and warfarin (100%). CONCLUSION: NOACs were at least as effective as warfarin, but more safer in Asians with AF. Apixaban was superior to other NOACs for reducing stroke or systemic embolism, while edoxaban showed a better safety profile than other NOACs.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Administração Oral , Idoso , Antitrombinas/uso terapêutico , Ásia/epidemiologia , Grupo com Ancestrais do Continente Asiático/etnologia , Efeitos Psicossociais da Doença , Dabigatrana/uso terapêutico , Embolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/prevenção & controle , Humanos , Masculino , Metanálise em Rede , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Segurança , Acidente Vascular Cerebral/epidemiologia , Tiazóis/uso terapêutico
10.
Sci Rep ; 10(1): 12221, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699227

RESUMO

Functional tests for lupus anticoagulants (LA) as part of a thrombophilia workup are commonly performed in patients under anticoagulant therapy that may interfere with assay results. There is no consensus on how these tests should be assessed in patients on direct oral anticoagulants (DOACs). In this retrospective cohort study, we analysed data from patients with a history of thrombosis in whom dilute Russell viper venom time (dRVVT), LA-sensitive aPTT, and solid phase assays for antiphospholipid antibodies (aPL) were performed (n = 3,147, thereof 588 on rivaroxaban, 144 on apixaban, 1,179 on other anticoagulant drugs). The dRVVT ratio was correlated with rivaroxaban (r = 0.30, P < 10-4) but not with apixaban plasma levels. The LA-sensitive aPTT/aPTT ratio showed no correlation with DOAC levels. Correspondingly, the rate of patients with abnormal dRVVT test was significantly higher (P < 10-4) under rivaroxaban (88%) than in thrombosis patients without anticoagulant medication (6%), independent from their aPL plasma levels. No isolated positive results of functional LA testing in patients on anticoagulants could be confirmed in repeated testing after discontinuation of the medication (n = 40). These data indicate that rivaroxaban should be discontinued before functional LA testing is performed. However, viable interpretation of these tests appears to be less affected in patients on apixaban.


Assuntos
Anticoagulantes/uso terapêutico , Inibidor de Coagulação do Lúpus/uso terapêutico , Trombose/tratamento farmacológico , Administração Oral , Adulto , Anticorpos Antifosfolipídeos/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea/métodos , Dabigatrana/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/métodos , Tempo de Protrombina/métodos , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Estudos Retrospectivos , Rivaroxabana/uso terapêutico , Trombofilia/tratamento farmacológico
11.
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
12.
Medicine (Baltimore) ; 99(21): e20200, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481289

RESUMO

RATIONALE: Idarucizumab is a specific reversal agent for patients with bleeding related to the anticoagulant dabigatran. There are no prior descriptions of Idarucizumab administration in the prehospital setting for intracranial hemorrhage. PATIENT CONCERNS: An 82-year-old woman treated with dabigatran for atrial fibrillation developed acute focal weakness. This led to activation of emergency medical services and assessment in the mobile stroke unit (MSU). DIAGNOSIS: Computed tomography of the brain performed in the MSU revealed an acute subdural hematoma. INTERVENTIONS: The patient was treated with Idarucizumab in the MSU. OUTCOMES: The subdural hematoma was treated with a burr hole evacuation and the patient was discharged to a rehabilitation facility without residual focal neurological deficits. LESSONS: Idarucizumab can be used safely and effectively to treat dabigatran-associated intracranial hemorrhage in the prehospital setting.


Assuntos
Antitrombinas/efeitos adversos , Dabigatrana/efeitos adversos , Hematoma Subdural/induzido quimicamente , Hematoma Subdural/tratamento farmacológico , Administração Intravenosa , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antitrombinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Serviços Médicos de Emergência , Feminino , Hematoma Subdural/diagnóstico por imagem , Hematoma Subdural/cirurgia , Humanos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Trepanação/métodos
13.
Am J Med ; 133(11): 1266-1273.e6, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32565258

RESUMO

The off-label use of direct oral anticoagulants (DOACs) for the treatment of left ventricular thrombi has grown over the past several years given the ease of administration, absence of a requirement for international normalized ratio (INR) monitoring, and freedom from dietary restrictions; however, the evidence for their safety and efficacy is contradictory. We systematically searched PubMed and Google Scholar from January 1, 2009, to April 25, 2020, for studies of DOACs for treatment of left ventricular thrombi. Fifty-three articles (of 1,168 patients) met our inclusion criteria. We found that the studies have reached conflicting results; based on our findings, their routine use for the treatment of left ventricular thrombi cannot be recommended. Adequately powered randomized controlled trials are needed to determine the safest and most effective treatment for left ventricular thrombi.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Cardiopatias/tratamento farmacológico , Ventrículos do Coração , Trombose/tratamento farmacológico , Dabigatrana/uso terapêutico , Humanos , Uso Off-Label , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento
14.
J Glaucoma ; 29(8): e87-e90, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32568812

RESUMO

PURPOSE: To describe a case of delayed-onset hemorrhagic choroidal detachment (HCD) in a patient affected by primary open-angle glaucoma (POAG) undergone PreserFlo Microshunt implantation. CASE REPORT DESCRIPTION: A 76-year-old patient with POAG, under treatment with Dabigatran (a novel oral anticoagulant), underwent an uncomplicated PreserFlo Microshunt implantation in the left eye. In the first postoperative day, intraocular pressure (IOP) was 6 mm Hg, conjunctival bleb was diffuse, anterior chamber (AC) deep, and device correctly positioned. Twelve days after surgery, the patient had emergency access complaining severe ocular pain and sudden vision loss. Ophthalmological evaluation revealed shallow AC and an IOP of 50 mm Hg. The fundus examination revealed almost kissing HCD. OUTCOME: Immediate topical treatment with atropine, aqueous humor suppressants, and corticosteroids was started. Because of high IOP, ocular pain, and the presence of almost kissing HCD, surgical drainage of suprachoroidal hemorrhage and removal of PreserFlo Microshunt were performed. An improvement of the clinical condition was observed in the following postoperative days, with partial resolution of the HCD and a decrease of the IOP. On the third postoperative day, there was a worsening of the HCD, with a reduction of the AC depth and IOP elevation. HCD was drained through the previously performed sclerotomies, associated with pars-plana vitrectomy and silicone-oil tamponade. HCD completely resolved during the following 6 weeks, with IOP reduction and partial improvement of visual acuity. CONCLUSION: Great attention must be taken in patients with glaucoma under treatment with a novel oral anticoagulant, also when planning PreserFlo Microshunt implantation.


Assuntos
Antitrombinas/uso terapêutico , Hemorragia da Coroide/etiologia , Efusões Coroides/etiologia , Dabigatrana/uso terapêutico , Implantes para Drenagem de Glaucoma/efeitos adversos , Glaucoma de Ângulo Aberto/cirurgia , Idoso , Anti-Hipertensivos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Atropina/uso terapêutico , Betametasona/uso terapêutico , Hemorragia da Coroide/diagnóstico , Hemorragia da Coroide/tratamento farmacológico , Efusões Coroides/diagnóstico , Efusões Coroides/tratamento farmacológico , Quimioterapia Combinada , Glaucoma de Ângulo Aberto/fisiopatologia , Glucocorticoides/uso terapêutico , Humanos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Masculino , Midriáticos/uso terapêutico , Implantação de Prótese/efeitos adversos , Tonometria Ocular
15.
Drugs Aging ; 37(7): 539-548, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32500503

RESUMO

INTRODUCTION: Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019. METHODS: A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA. RESULTS: A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A. CONCLUSION: OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Assistência de Longa Duração/métodos , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Conferências de Consenso como Assunto , Dabigatrana/administração & dosagem , Dabigatrana/uso terapêutico , Europa (Continente) , Feminino , Humanos , Masculino , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana/administração & dosagem , Rivaroxabana/uso terapêutico , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Varfarina/uso terapêutico
16.
Stroke ; 51(7): 2066-2075, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32539675

RESUMO

BACKGROUND AND PURPOSE: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. METHODS: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. RESULTS: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. CONCLUSIONS: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Adulto , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Embolia/tratamento farmacológico , Embolia/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Varfarina/efeitos adversos , Varfarina/uso terapêutico
17.
Biochem Biophys Res Commun ; 527(2): 532-538, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32423817

RESUMO

Parkinson's disease (PD) is a complex neurodegenerative disease characterized by the presence of tremors, loss of dopaminergic neurons and accumulation of α-synuclein. While there is no single direct cause of PD, genetic mutations, exposure to pesticides, diet and traumatic brain injury have been identified as risk factors. Increasing evidence suggests that oxidative stress and neuroinflammation contribute to the pathogenesis of neuronal injury in neurodegenerative diseases such as PD and Alzheimer's disease (AD). We have previously documented that the multifunctional inflammatory mediator thrombin contributes to oxidative stress and neuroinflammation in AD. Here, for the first time, we explore the role of thrombin in a transgenic PD model, the LRRK2 mutant Drosophila melanogaster. Transgenic flies were treated with the direct thrombin inhibitor dabigatran for 7 days and locomotor activity and indices of oxidative stress evaluated. Our data show that dabigatran treatment significantly (p < 0.05) improved climbing activity, a measurement of locomotor ability, in male but had no effect on locomotor performance in female flies. Dabigatran treatment had no effect on tyrosine hydroxylase levels. Analysis of oxidative stress in male flies showed that dabigatran was able to significantly (p < 0.01) lower reactive oxygen species levels. Furthermore, Western blot analysis showed that the pro-oxidant proteins iNOS and NOX4 are elevated in LRRK2 male flies compared to wildtype and that treatment with dabigatran reduced expression of these proteins. Our results indicate that dabigatran treatment could improve motor function in PD by reducing oxidative stress. These data suggest that targeting thrombin may improve oxidative stress related pathologies in PD.


Assuntos
Antitrombinas/uso terapêutico , Dabigatrana/uso terapêutico , Drosophila melanogaster/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/fisiologia , Modelos Animais de Doenças , Drosophila melanogaster/fisiologia , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Locomoção/efeitos dos fármacos , Masculino , Mutação , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Trombina/metabolismo
18.
Am J Cardiol ; 126: 29-36, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32359718

RESUMO

It remains unknown whether the comparative effectiveness of direct oral anticoagulants (DOACs) and warfarin differs between atrial fibrillation patients with and without a history of stroke or transient ischemic attack (TIA). Using 2012 to 2014 Medicare claims data, we identified patients newly diagnosed with AF in 2013 to 2014 who initiated apixaban, dabigatran, rivaroxaban, or warfarin. We categorized patients based on a history of stroke or TIA. We constructed Cox proportional hazard models that included indicator variables for treatment groups, a history of stroke or TIA, and the interaction between them, and controlled for demographics and clinical characteristics. DOACs were generally more effective than warfarin in stroke prevention; however, there were important differences between subgroups defined by a history of ischemic stroke. In particular, the superiority of dabigatran compared with warfarin in ischemic stroke prevention was more pronounced in patients with a history of stroke or TIA (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.48 to 0.85) than in patients with no history of stroke or TIA (HR 0.94; 95% CI 0.75 to 1.16; p value for interaction = 0.034). There was no difference in the risk of stroke between apixaban, dabigatran, and rivaroxaban in patients with no history of stroke or TIA. However, in patients with a history of stroke or TIA, the risk of stroke was lower with dabigatran (HR 0.64; 95% CI 0.48 to 0.85) and rivaroxaban (HR 0.70; 95% CI 0.56 to 0.87), compared with apixaban (p value for both interactions <0.05). In conclusion, the comparative effectiveness of DOACs differs substantially between patients with and without a history of stroke or TIA; specifically, apixaban is less effective in patients with a history of stroke or TIA.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico , Idoso , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/prevenção & controle , Masculino , Medicare , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Estados Unidos/epidemiologia
19.
Ann Intern Med ; 173(1): 1-9, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32423351

RESUMO

BACKGROUND: It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF). OBJECTIVE: To compare the risk for osteoporotic fracture between anticoagulants. DESIGN: Population-based cohort study. SETTING: Territory-wide electronic health record database of the Hong Kong Hospital Authority. PARTICIPANTS: Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018. MEASUREMENTS: Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score-weighted cumulative incidence differences (CIDs). RESULTS: There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, -0.88% [95% CI, -1.66% to -0.21%]; dabigatran CID, -0.81% [CI, -1.34% to -0.23%]; and rivaroxaban CID, -1.13% [CI, -1.67% to -0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, -0.06% [CI, -0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, -0.32% [CI, -0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, -0.25% [CI, -0.86% to 0.40%]). LIMITATION: Residual confounding is possible. CONCLUSION: Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit-risk assessment when choosing between anticoagulants. PRIMARY FUNDING SOURCE: The University of Hong Kong and University College London Strategic Partnership Fund.


Assuntos
Dabigatrana/uso terapêutico , Fraturas por Osteoporose/epidemiologia , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Estudos de Coortes , Feminino , Seguimentos , Fraturas do Quadril/epidemiologia , Hong Kong/epidemiologia , Humanos , Masculino , Fraturas da Coluna Vertebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
20.
Am J Med ; 133(11): 1302-1312, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32389658

RESUMO

BACKGROUND: Body mass index (BMI) affects drug levels of nonvitamin K antagonist oral anticoagulants. We sought to assess whether BMI affected outcomes in the RE-DUAL PCI trial. METHODS: RE-DUAL PCI (NCT02164864) evaluated the safety and efficacy of a dual-antithrombotic-therapy regimen using dabigatran (110 mg or 150 mg twice daily and a P2Y12 platelet antagonist) in comparison with triple therapy of warfarin, aspirin, and a P2Y12 platelet inhibitor in 2725 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI). We compared the risk of first International Society on Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant nonmajor bleeding events (primary endpoint) and the composite of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization (main efficacy endpoint) in relation to baseline BMI. RESULTS: Median (range) BMI was 28.1 (14-66) kg/m2. Dabigatran dual therapy versus warfarin triple therapy had relevantly and similarly lower rates of bleeding at both 110 mg and 150 mg twice-daily doses, irrespective of BMI. Thromboembolic event rates appeared consistent across categories of BMI, including those <25 and ≥35 kg/m2 (P for interaction: 0.806 and 0.279, respectively). CONCLUSIONS: The reduction in bleeding with dabigatran dual therapy compared with warfarin triple therapy in patients here evaluated appears consistent across BMI categories.


Assuntos
Antitrombinas/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Doença da Artéria Coronariana/cirurgia , Dabigatrana/uso terapêutico , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/complicações , Quimioterapia Combinada , Terapia Antiplaquetária Dupla , Embolia/epidemiologia , Embolia/etiologia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Cuidados Pós-Operatórios , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Ticagrelor/uso terapêutico
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