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1.
Ther Adv Cardiovasc Dis ; 13: 1753944719863641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364490

RESUMO

BACKGROUND: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. METHODS: A post hoc exposure-response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. RESULTS: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06-1.11 (95th percentile versus median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38-0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44-0.87 (no versus yes)]. CONCLUSIONS: The shallow slopes of the exposure-response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Modelos Biológicos , Rivaroxabana/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Isquemia Encefálica/mortalidade , Tomada de Decisão Clínica , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacocinética , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinética , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento
2.
Expert Rev Clin Pharmacol ; 12(8): 771-780, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31269825

RESUMO

Introduction: The current approach of using only antiplatelet therapy for secondary prevention leaves a substantial risk of recurrent cardiovascular complications and mortality. Areas covered: In this manuscript, the role of coagulation in atherothrombosis is reviewed, as well as the impact of vascular doses of rivaroxaban on major cardiovascular outcomes and major adverse limb events. Expert opinion: In COMPASS, among patients with coronary heart disease and/or peripheral artery disease, compared to aspirin, the addition of rivaroxaban 2.5 mg twice daily to aspirin, significantly reduced the risk of major atherosclerotic outcomes, cardiovascular death and death for any cause, with a significant increase in the risk of major bleeding, but not fatal or intracranial bleedings. Preclinical data strongly suggest that rivaroxaban exerts vascular protection through different mechanisms, including improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties, and platelet-dependent thrombin generation. All these data indicate that among patients with atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg may provide further vascular protection.


Assuntos
Aterosclerose/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Animais , Aspirina/administração & dosagem , Aterosclerose/patologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacologia , Hemorragia/induzido quimicamente , Humanos , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacologia , Prevenção Secundária/métodos
3.
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
4.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
5.
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
6.
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
9.
Angiology ; 70(10): 896-907, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31010298

RESUMO

Factor Xa (FXa) is the key serine protease of the coagulation cascade as it is the point of convergence of the intrinsic and extrinsic pathways, leading to the formation of thrombin. Factor Xa is an established target of anticoagulation therapy, due to its central role in coagulation. Over the past years, several direct oral anticoagulants (DOACs) targeting FXa have been developed. Rivaroxaban, apixaban, and edoxaban are used in clinical practice for prevention and treatment of thrombotic diseases. Increasing evidence suggests that FXa exerts nonhemostatic cellular effects that are mediated mainly through protease-activated receptors-1 and -2 and are involved in pathophysiological conditions, such as atherosclerosis, inflammation, and fibrosis. Direct inhibition of FXa by DOACs could be beneficial in these conditions. This is a narrative review that focuses on the cellular effects of FXa in various cell types and conditions, as well as on the possible pleiotropic effects of FXa-targeting DOACs.


Assuntos
Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/uso terapêutico , Fator Xa/efeitos dos fármacos , Administração Oral , Animais , Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Humanos , Trombina/efeitos dos fármacos
10.
Braz J Med Biol Res ; 52(4): e8006, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30970082

RESUMO

The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=-0.771, P<0.001), amplitude after 5 min (rho=-0.763, P<0.001), and amplitude after 10 min (rho=-0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.


Assuntos
Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/sangue , Hemorragia/prevenção & controle , Rivaroxabana/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Cromatografia Líquida de Alta Pressão , Confiabilidade dos Dados , Inibidores do Fator Xa/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/administração & dosagem , Espectrometria de Massas em Tandem , Tromboelastografia
11.
J Card Surg ; 34(6): 419-423, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31012168

RESUMO

BACKGROUND: Novel oral anticoagulants (NOAC) have been shown to have comparable risk profiles compared with warfarin. However, data on the use of NOACs in cardiac surgery patients is limited. The aim of this study is to compare postoperative effusion rates in patients who were anticoagulated with NOACs vs warfarin after coronary artery bypass grafting (CABG). METHODS: A retrospective review of 2017 patients undergoing isolated CABG from 2014 to 2017 was performed. Of those patients, 246 patients (12.2%) were placed on either a NOAC or warfarin postoperatively. The combined rates of postoperative pericardial and pleural effusions requiring invasive intervention during the index hospitalization and up to 3 months postoperatively were compared between patients who were placed on NOACs vs warfarin. RESULTS: Of the 246 patients placed on oral anticoagulation after isolated CABG, 64 (26.0%) were placed on NOACs, and 182 (74.0%) received warfarin. There were no significant differences in preoperative coagulation profile and use of anticoagulation and antiplatelets preoperatively between the groups. Of the patients anticoagulated with NOACs postoperatively, 17 patients (26.6%) required invasive interventions for effusions compared with 24 patients (13.2%) in the cohort anticoagulated with warfarin (P < 0.014). Of the patients who required interventions for effusions, those on NOACs were more likely to require delayed interventions compared with those on warfarin. CONCLUSIONS: Patients receiving NOACs after CABG are at increased risk of developing effusions requiring invasive interventions compared to patients receiving warfarin. This increased risk should be taken into consideration when choosing the appropriate anticoagulation strategy for postoperative patients with CABG.


Assuntos
Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Ponte de Artéria Coronária , Inibidores do Fator Xa/administração & dosagem , Derrame Pericárdico/prevenção & controle , Derrame Pleural/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Retrospectivos , Risco
12.
BMJ Case Rep ; 12(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940667

RESUMO

A 63-year-old woman with known antiphospholipid syndrome (APLS) presented with catastrophic APLS and multiorgan dysfunction after a change in her anticoagulation from warfarin to rivaroxaban. Evidence suggests direct-acting oral anticoagulants (DOACs) like rivaroxaban may be less effective than warfarin in secondary prevention of thrombotic events in high-risk APLS patients.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Rivaroxabana/administração & dosagem , Prevenção Secundária , Trombose/prevenção & controle , Administração Oral , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Trombose/etiologia , Varfarina/uso terapêutico
13.
Vasc Endovascular Surg ; 53(5): 408-410, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30913995

RESUMO

INTRODUCTION: Venous thromboembolism (VTE) of the lower extremities frequently occurs after surgery. It is unknown whether the complication of renal vein thrombosis (RVT) develops after an open repair (OR) for abdominal aortic aneurysm (AAA). Furthermore, anticoagulation therapy with apixaban, a direct oral anticoagulant (DOAC), has not been described as treatment for RVT in such cases. CASE: A 64-year-old man underwent OR for AAA. Postoperative computed tomography revealed RVT in the left renal vein. Apixaban (5 mg twice a day) therapy was initiated. Six months later, we discontinued anticoagulation therapy and observed no recurrence. Following OR, our patient developed RVT for which DOACs were very useful. CONCLUSION: Thus, RVT can manifest as VTE after OR and direct anticoagulants can be considered as a therapeutic option.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Inibidores do Fator Xa/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Veias Renais/efeitos dos fármacos , Grau de Desobstrução Vascular/efeitos dos fármacos , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Trombose Venosa/tratamento farmacológico , Administração Oral , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Humanos , Masculino , Pessoa de Meia-Idade , Flebografia/métodos , Veias Renais/diagnóstico por imagem , Veias Renais/fisiopatologia , Resultado do Tratamento , Ultrassonografia Doppler em Cores , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
14.
J Vet Intern Med ; 33(3): 1322-1330, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30859645

RESUMO

BACKGROUND: The chromogenic anti-Xa assay, the gold standard for monitoring the anti-Xa effect of rivaroxaban, is not available as a cage-side diagnostic test for use in a clinical setting. HYPOTHESIS/OBJECTIVES: To evaluate clinical modalities for measuring the anticoagulant effects of rivaroxaban using a point-of-care prothrombin time (PT) and thromboelastography (TEG). ANIMALS: Six healthy Beagle dogs. METHODS: Prospective, experimental study. Four different doses of rivaroxaban (0.5, 1, 2, and 4 mg/kg) were administered PO to dogs. Single PO and 3 consecutive dosing regimens also were assessed. Plasma rivaroxaban concentration was determined using a chromogenic anti-Xa assay, point-of-care PT, and TEG analysis with 4 activators (RapidTEG, 1 : 100 tissue factor [TF100], 1 : 3700 tissue factor [TF3700], and kaolin), and results were compared. Spearman correlation coefficients were calculated between ratios (peak to baseline PT; peak reaction time [R] of TEG to baseline [R] of TEG) and anti-Xa concentration. RESULTS: Anti-Xa concentration had a significant correlation with point-of-care PT (R = 0.82, P < .001) and RapidTEG-TEG, TF100-TEG, and TF3700-TEG (R = 0.76, P < .001; R = 0.82, P < .001; and R = 0.83, P < .001, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Overall, a 1.5-1.9 × delay in PT and R values of TEG 3 hours after rivaroxaban administration is required to achieve therapeutic anti-Xa concentrations of rivaroxaban in canine plasma. The R values of TEG, specifically using tissue factors (RapidTEG, TF100, TF3700) and point-of-care PT for rivaroxaban can be used practically for therapeutic monitoring of rivaroxaban in dogs.


Assuntos
Inibidores do Fator Xa/farmacologia , Tempo de Protrombina/veterinária , Rivaroxabana/farmacologia , Tromboelastografia/veterinária , Animais , Cães/sangue , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/farmacocinética , Masculino , Estudos Prospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/farmacocinética
15.
Medicine (Baltimore) ; 98(12): e14821, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30896626

RESUMO

RATIONALE: The efficacy of direct oral anticoagulants (DOACs) in the treatment and prophylaxis of cancer-related venous thromboembolism (VTE) is reportedly similar to that of heparin. However, the effect of DOACs on the prophylaxis of cancer-related arterial thromboembolism (ATE) remains unclear. To our knowledge, we present the 1st case where cerebral ATE was encountered during edoxaban administration for VTE in a patient with lung adenocarcinoma. PATIENT CONCERNS: In March 2017, a 63-year-old female was diagnosed with lung adenocarcinoma (cT2aN3M1b stage IVa) along with having asymptomatic VTE; thus, 60 mg/day edoxaban administration was initiated. In addition, 1st-line chemotherapy generated a partial antitumoral response. However, owing to lung cancer progression, a secondary treatment with pembrolizumab administration was initiated. The patient suddenly experienced aphasia 11 days after pembrolizumab administration. DIAGNOSIS: The patient was diagnosed as multiple cerebral ATE using brain magnetic resonance imaging. However, VTE recurrence was not observed. Based on the findings of lung cancer progression and increased coagulation, cerebral ATE was diagnosed as Trousseau syndrome. INTERVENTIONS: DOAC administration was switched to heparin administration. OUTCOMES: Coagulation profile normalized and aphasia improved without any further disease symptoms. LESSONS: We considered that DOACs are effective for the treatment and prophylaxis of VTE but may be insufficient for ATE prevention. Therefore, DOACs should be replaced with heparin to prevent ATE when cancer and coagulation become uncontrollable with DOAC.


Assuntos
Adenocarcinoma/complicações , Inibidores do Fator Xa/efeitos adversos , Embolia Intracraniana/induzido quimicamente , Neoplasias Pulmonares/complicações , Piridinas/efeitos adversos , Tiazóis/efeitos adversos , Tromboembolia Venosa/complicações , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Progressão da Doença , Inibidores do Fator Xa/administração & dosagem , Feminino , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Humanos , Embolia Intracraniana/tratamento farmacológico , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Tiazóis/administração & dosagem , Tromboembolia Venosa/prevenção & controle
17.
J Thromb Thrombolysis ; 47(3): 345-352, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790160

RESUMO

Warfarin is dependent on multiple hepatic enzymes for metabolism while apixaban is a substrate for P-glycoprotein (P-gp) transport and hepatic CYP3A4 metabolism. The aim of this analysis was to assess the impact of interacting medication use on the treatment effects of apixaban versus warfarin. Outcomes were compared between apixaban and warfarin using Cox proportional hazards modeling according to the use of interacting medications at randomization in ARISTOTLE (n = 18,201). Interacting medications for apixaban were identified as combined P-gp and 3A4 inhibitors or inducers while interacting medications for warfarin were defined as those highly probable for warfarin potentiation or inhibition. At randomization, 5547 (30.5%) patients were on an interacting medication, including 2722 on apixaban and 2825 on warfarin. Patients using an interacting medication were more likely to be female, taking aspirin, and have a history of prior bleeding and were less likely to have a prior stroke or transient ischemic attack. No significant differences were observed on the treatment effect of apixaban compared with warfarin in patients on and off interacting medications for outcomes including the primary efficacy outcome of stroke or systemic embolism (P for interaction = 0.79) or the primary safety outcome of major bleeding (P for interaction = 0.75). Use of interacting medications with anticoagulants occurs often in patients with atrial fibrillation. Despite the potential for altered exposure, interacting medication use was not associated with a significant change in the efficacy or safety of apixaban compared with warfarin in the ARISTOTLE trial.Trial registration ClinicalTrials.gov, NCT00412984.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Interações de Medicamentos , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Varfarina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Embolia/induzido quimicamente , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Resultado do Tratamento , Varfarina/efeitos adversos , Adulto Jovem
18.
Circ Res ; 124(3): 426-436, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30702990

RESUMO

Recent advances in our understanding of the contribution of thrombin generation to arterial thrombosis and the role of platelets in venous thrombosis have prompted new treatment paradigms. Nonetheless, bleeding remains the major side effect of such treatments spurring the quest for new antithrombotic regimens with better benefit-risk profiles and for safer anticoagulants for existing and new indications. The aims of this article are to review the results of recent trials aimed at enhancing the benefit-risk profile of antithrombotic therapy and explain how these findings are changing our approach to the management of arterial and venous thrombosis. Focusing on these 2 aspects of thrombosis management, this article discusses 4 advances: (1) the observation that in some indications, lowering the dose of some direct oral anticoagulants reduces the risk of bleeding without compromising efficacy, (2) the recognition that aspirin is not only effective for secondary prevention of atherothrombosis but also for prevention of venous thromboembolism, (3) the finding that dual pathway inhibition with the combination of low-dose rivaroxaban to attenuate thrombin generation plus aspirin to reduce thromboxane A2-mediated platelet activation is superior to aspirin or rivaroxaban alone for prevention of atherothrombosis in patients with coronary or peripheral artery disease, and (4) the development of inhibitors of factor XI or XII as potentially safer anticoagulants.


Assuntos
Aspirina/uso terapêutico , Inibidores do Fator Xa/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/administração & dosagem , Trombose/tratamento farmacológico , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Fibrilação Atrial/complicações , Ensaios Clínicos como Assunto , Doença das Coronárias/complicações , Quimioterapia Combinada , Fator XI/antagonistas & inibidores , Fator XII/antagonistas & inibidores , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Doença Arterial Periférica/complicações , Placa Aterosclerótica/complicações , Agregação Plaquetária , Prevenção Primária , Medição de Risco , Prevenção Secundária , Trombina/metabolismo , Trombose/etiologia , Trombose/prevenção & controle , Trombose Venosa/prevenção & controle
19.
Circ Res ; 124(3): 416-425, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30702997

RESUMO

Although acetylsalicylic acid is of proven benefit for secondary prevention in patients with cardiovascular disease, the risk of recurrent ischemic events remains high. Intensification of antithrombotic therapy with more potent antiplatelet drugs, dual antiplatelet therapy, or vitamin K antagonists further reduces the risk of major adverse cardiovascular events compared with acetylsalicylic acid alone but increases the risk of bleeding without reducing mortality. In patients with prior coronary artery disease or peripheral arterial disease the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial revealed that compared with acetylsalicylic acid alone, dual pathway inhibition with low-dose rivaroxaban (2.5 mg twice-daily), an oral factor Xa inhibitor, plus acetylsalicylic acid reduced major adverse cardiovascular event by 24%, major adverse limb events by 47%, and mortality by 18%. Major bleeding was increased by 70%, but there was no increase in fatal or intracranial bleeding. This article (1) reviews the results of the COMPASS trial, (2) explains why dual pathway inhibition is superior to antiplatelet or anticoagulant therapy alone, (3) compares the results with rivaroxaban plus aspirin with those with other antithrombotic regimens, and (4) provides insight into how best to apply the COMPASS results into practice.


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Doença Crônica , Doença da Artéria Coronariana/tratamento farmacológico , Quimioterapia Combinada/métodos , Inibidores do Fator Xa/administração & dosagem , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Recidiva , Projetos de Pesquisa , Rivaroxabana/administração & dosagem , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle
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