Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 159
Filtrar
1.
N Engl J Med ; 382(2): 130-139, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733182

RESUMO

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).


Assuntos
Valva Aórtica/fisiopatologia , Aspirina/farmacologia , Clopidogrel/farmacologia , Inibidores do Fator Xa/farmacologia , Próteses Valvulares Cardíacas , Inibidores da Agregação de Plaquetas/farmacologia , Rivaroxabana/farmacologia , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/patologia , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Tomografia Computadorizada Quadridimensional , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Tromboembolia/etiologia , Tromboembolia/mortalidade
2.
J Assoc Physicians India ; 67(11): 60-65, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31793271

RESUMO

Oral anticoagulants are commonly prescribed in patients with kidney diseases having atrial fibrillation and thromboembolic risk. It is very important to understand their clinical pharmacology and changes that may occur as GFR declines. Risks and benefits of newer oral anticoagulants are different in patients with CKD and patients with ESRD. Patients with GFR < 30 ml/min per 1.73 m2, including those on dialysis, were systematically excluded from landmark trials. All of the NOACs are dependent on renal clearance to some degree and so the risk of NOAC associated bleeding may be expected to be greater in patients with renal failure. Apixaban may be at least as safe as (or possibly safer than) warfarin in individuals with ESRD. Until more data become available, use of dabigatran, rivaroxaban, and edoxaban in patients with CKD stage 5 and ESRD is not indicated. Available strategies for reversing the anticoagulant effect of NOAC are - specific reversal agents available for dabigatran (idarucizumab) and for the oral direct factor Xa inhibitors - andexanet alfa, antifibrinolytic agents, DDAVP and prothrombin complex concentrates (PCCs). In this review clinical and pharmacological aspects of newer oral anticoagulants in the setting of chronic kidney disease will be discussed.


Assuntos
Anticoagulantes , Fibrilação Atrial , Insuficiência Renal Crônica , Administração Oral , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Inibidores do Fator Xa , Humanos , Insuficiência Renal Crônica/complicações , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico
3.
Angiol Sosud Khir ; 25(4): 35-39, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31855199

RESUMO

The authors analysed oral anticoagulant agents prescribed in the postoperative period to patients after endured reconstructive operative intervention on arteries of the femorotibial segment. The study included a total of 104 patients subjected to femoropopliteal or femorotibial bypass grafting using an autologous vein or a prosthesis. Depending on the prescribed anticoagulation agent, the patients were subdivided into two groups. Group One patients (n=43) in the postoperative period received rivaroxaban, and Group Two patients (n=61) took warfarin. Efficacy of therapy was evaluated by the frequency of haemorrhage and thromboses in the early and remote postoperative periods. The findings of the immediate postoperative period demonstrated comparable rates of haemorrhagic complications, early thromboses and redo interventions in both Groups (p=0.7). The duration of long-term postoperative period varied from 3 months to 5 years. No statistically significant differences in patency of the performed reconstructions were revealed between the groups. The 3-year primary assisted patency rate in the rivaroxaban group and warfarin group amounted to 89 and 80%, respectively. The incidence of haemorrhagic complications in the postoperative period was insignificant in the studied groups. Hence, rivaroxaban may be prescribed in the early and remote postoperative period to patients who underwent open reconstructive operative intervention on arteries of the infrainguinal zone.


Assuntos
Anticoagulantes/uso terapêutico , Rivaroxabana/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/cirurgia , Grau de Desobstrução Vascular/efeitos dos fármacos , Varfarina/uso terapêutico , Anticoagulantes/farmacologia , Artérias/efeitos dos fármacos , Artérias/cirurgia , Implante de Prótese Vascular , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/cirurgia , Humanos , Extremidade Inferior/irrigação sanguínea , Artéria Poplítea/efeitos dos fármacos , Artéria Poplítea/cirurgia , Estudos Retrospectivos , Rivaroxabana/farmacologia , Artérias da Tíbia/efeitos dos fármacos , Artérias da Tíbia/cirurgia , Resultado do Tratamento , Varfarina/farmacologia
4.
J Plast Surg Hand Surg ; 53(6): 370-380, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31478782

RESUMO

The application of venous thromboembolism (VTE) prophylaxis has been the topic of intense debate in plastic surgery. The overall incidence of VTE is low in plastic surgery patients as compared to other surgical subspecialties but may be higher in the inpatient rather than outpatient plastic surgery populations. The Caprini Risk Assessment Model is the most highly studied and validated tool to assess VTE risk in plastic surgery patients. However, the Caprini model lacks procedure-specific risk assessment and patient-specific risk factor calculations. Due to these limitations, such as the low incidence and the heterogeneous nature of the specialty, trials lacked the power to capture proof of benefit, except in the highest-risk inpatient population. The emerging use of aspirin and novel oral anticoagulants may provide an alternative, as noninferiority in terms of efficacy and safety has been demonstrated in other fields. In this review, the authors intend to summarize the current state of evidence for prevention and explore the modalities available for prophylaxis, including novel oral anticoagulants.


Assuntos
Anticoagulantes/uso terapêutico , Quimioprevenção , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Medição de Risco , Tromboembolia Venosa/prevenção & controle , Administração Oral , Anticoagulantes/farmacologia , Aspirina/farmacologia , Aspirina/uso terapêutico , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Incidência , Complicações Pós-Operatórias , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridonas/farmacologia , Piridonas/uso terapêutico , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico
5.
Clin Appl Thromb Hemost ; 25: 1076029619868535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31392894

RESUMO

Warfarin has been associated with renovascular calcification and worsening renal function, whereas rivaroxaban may provide a degree of renopreservation by decreasing vascular inflammation. We sought to compare rivaroxaban and warfarin's impact on renal decline in patients with nonvalvular atrial fibrillation (NVAF) treated in routine practice. Using US MarketScan claims data from January 2012 to December 2017, we identified patients with NVAF newly initiated on rivaroxaban or warfarin with ≥12 months of continuous insurance coverage prior to initiation. Patients with stage 5 chronic kidney disease (CKD) or receiving hemodialysis at baseline were excluded. Outcomes included rates (events/100 person-years) of hospital or emergency department admission for acute kidney injury (AKI) or progression to stage 5 CKD or need for hemodialysis. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until an event, anticoagulant discontinuation/switch, insurance disenrollment, or end of data availability. Hazard ratios with 95% confidence intervals (CIs) were estimated using Cox regression. We assessed 36 318 rivaroxaban (19.8% received a dose <20 mg/d) and 36 281 warfarin users. Stages 3 and 4 CKD were present in 5% and 1% of patients at baseline, and proteinuria was present in 2%. Rivaroxaban was associated with a 19% (95% CI = 13%-25%) reduction in the hazard of AKI (rates = 4.91 vs 8.45) and an 18% (95% CI = 9%-26%) reduction in progression to stage 5 CKD or hemodialysis (rates = 2.67 vs 4.12). Rivaroxaban appears associated with lower hazards of undesirable renal end points versus warfarin in patients with NVAF.


Assuntos
Fibrilação Atrial/complicações , Rim/efeitos dos fármacos , Rivaroxabana/uso terapêutico , Lesão Renal Aguda/prevenção & controle , Idoso , Fibrilação Atrial/tratamento farmacológico , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Rim/fisiopatologia , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Estudos Retrospectivos , Rivaroxabana/farmacologia , Varfarina/farmacologia , Varfarina/uso terapêutico
6.
Clin Appl Thromb Hemost ; 25: 1076029619863493, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31298056

RESUMO

Recombinant coagulation factor Xa (FXa), inactivated Zh-zo, also known as andexanet alfa (AA), is a modified version of human FXa that has been developed to neutralize FXa inhibitors. We studied the reversal effect of AA for these inhibitors in various anticoagulant and thrombin generation (TG) assays. Individual aliquots of normal human plasma containing 1 µg/mL of apixaban, betrixaban, edoxaban, and rivaroxaban, were supplemented with saline or AA at a concentration of 100 µg/mL. Clotting profiles include prothrombinase-induced clotting time, activated partial thromboplastin time, and prothrombin time. Factor Xa activity was measured using an amidolytic method. Thrombin generation was measured using a calibrated automated thrombogram. Differential neutralization of all 4 anticoagulants was noted in the activated clotting time and other clotting tests. The FXa activity reversal profile varied with an observed decrease in apixaban (22%), betrixaban (56%), edoxaban (28%), and rivaroxaban (49%). Andexanet alfa also led to an increased TG in comparison to saline. The peak thrombin was higher (40%), area under the curve (AUC) increased (15%), whereas the lag time (LT) decreased (17%). Andexanet alfa added at 100 µg/mL to various FXa supplemented systems resulted in reversal of the inhibitory effects, restoring the TG profile; AUC, LT, and peak thrombin levels were comparable to those of unsupplemented samples. Andexanet alfa is capable of reversing anti-Xa activity of different oral FXa inhibitors but overshoots thrombogenesis in both the saline and FXa inhibitor supplemented systems. The degree of neutralization of Xa inhibitor is specific to each agent.


Assuntos
Antagonismo de Drogas , Inibidores do Fator Xa/farmacologia , Fator Xa/farmacologia , Proteínas Recombinantes/farmacologia , Trombina/biossíntese , Anticoagulantes/farmacologia , Benzamidas/farmacologia , Testes de Coagulação Sanguínea , Inibidores do Fator Xa/química , Humanos , Pirazóis/farmacologia , Piridinas/farmacologia , Piridonas/farmacologia , Rivaroxabana/farmacologia , Tiazóis/farmacologia , Trombina/efeitos dos fármacos
7.
J Vasc Res ; 56(4): 181-190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266015

RESUMO

BACKGROUND: Coagulant factor Xa inhibitors (XaIs) are prescribed for patients with atrial fibrillation for years. METHODS: Human umbilical venous endothelial cells (HUVECs) were cultured with or without (w/wo) a XaI (rivaroxaban) under high glucose (HG: 22 mM). Endothelial senescence was investigated by assessing senescence-associated-ß-galactosidase (SA-ß-gal), p53, and telomere length. Endothelial function and atherosclerosis were examined by nitric oxide-related-products (NOx: NO2- and NO3-), O2-, endothelial NO synthase (eNOS), NADPH oxidase (p22phox), and ICAM1. PAR1 (protease-activated receptor 1) and PAR2, which were reported to regulate eNOS phosphorylation, were inhibited by small interfering RNAs (siRNAs). Thirty-two male dyslipidemic type 2 diabetic rats (ZFDM LepRfa/fa) were fed a high-cholesterol diet w/wo XaI (50 µg/day/kg) for 1-4 weeks. RESULTS: SA-ß-gal, p53, p21, and p16INK4a were increased by HG and restored by XaI (50 nM) in HUVECs. XaI restored telomerase activity and preserved telomere length. XaI suppressed O2-, p22phox, and ICAM1 and restored NOx and eNOS. XaI decreased PAR1 following elevation by HG, which was confirmed by PAR1 siRNA and PAR2 siRNA. In in vivo experiments, plasma glucose, total cholesterol, and triglycerides were increased for 4 weeks but were not changed by XaI. XaI decreased SA-ß-gal and telomerase and preserved telomere length in the aortic endothelium. XaI activated eNOS, inhibited p22phox, increased plasma NOx, and decreased O2-. CONCLUSION: Rivaroxaban prevents replicative senescence in HUVECs and aortic endothelial cells in dyslipidemic diabetic mice. It restores endothelial function and prevents the progression of atherosclerosis.


Assuntos
Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Inibidores do Fator Xa/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Rivaroxabana/farmacologia , Animais , Doenças da Aorta/sangue , Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Glicemia/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Lipídeos/sangue , Óxido Nítrico/metabolismo , Ratos Zucker , Espécies Reativas de Oxigênio/metabolismo , Receptores Ativados por Proteinase/metabolismo , Transdução de Sinais , Telomerase/metabolismo
8.
Thromb Haemost ; 119(9): 1419-1432, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31266079

RESUMO

The activation of protease-activated receptor (PAR)-2 by factor Xa (fXa) promotes the release of tissue factor-positive microvesicles (TF+MV), and contributes to proliferation in cancer cells. This study examined the ability of direct oral anticoagulants (DOACs), apixaban and rivaroxaban, to inhibit the release of TF+MV from two cell lines (MDA-MB-231 and AsPC-1) as well as cell proliferation.Activation of the cells with fXa (10 nM) enhanced the release of TF+MV but was suppressed in the presence of either DOAC. These MVs were found to contain fVIIa, but not fXa. Incubation of cell lines with apixaban (1.8 µM) but not rivaroxaban (1.8 µM), in the absence of fXa decreased the release of TF+MV below that of resting cells, in a PAR2-dependent manner. Furthermore, incubation with apixaban reduced the proliferation rate in both cells lines. Incubation of purified fVIIa with apixaban but not rivaroxaban resulted in complete inhibition of fVIIa proteolytic activity as measured using two fVIIa chromogenic substrates. Pre-incubation of the cells with an inhibitory anti-fVIIa antibody, with apixaban or the blocking of PAR2 suppressed the release of TF+MV to a comparable level, and reduced cell proliferation but the effect was not cumulative.This study has established that the activation of PAR2 by TF-fVIIa complex is the principal mediator in augmenting the release of TF+MV as well as cancer cell proliferation. Importantly, for the first time we have shown that apixaban selectively inhibits the proteolytic activity of fVIIa as well as the signalling arising from the TF-fVIIa complex.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Micropartículas Derivadas de Células/metabolismo , Inibidores do Fator Xa/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Pirazóis/farmacologia , Piridonas/farmacologia , Tromboplastina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Fator VIIa/metabolismo , Feminino , Humanos , Receptor PAR-2/metabolismo , Rivaroxabana/farmacologia , Transdução de Sinais
9.
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
10.
Thromb Res ; 181: 24-28, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31326717

RESUMO

INTRODUCTION: Direct oral anticoagulants (DOACs) have become widely used to treat patients with venous thromboembolism (VTE), but evidence about their use in the treatment of upper extremity deep vein thrombosis (UEDVT) is lacking. OBJECTIVES: To assess rivaroxaban's efficacy and safety in the treatment of UEDVT. PATIENTS/METHODS: This was a single-center prospective observational study involving patients with their first UEDVT episode confirmed by duplex ultrasound scan. All patients initially received low-molecular-weight heparin for 1 to 2 days and then were switched to rivaroxaban for 3-6 months. The primary endpoint was any symptomatic episode of recurrent VTE. RESULTS: Thirty patients were included in the study, and all patients were followed for 6 months. There were no episodes of recurrent symptomatic venous thromboembolism or asymptomatic UEDVT. No episode of major bleeding was observed. Clinically relevant non-major bleeding occurred in two patients (6.7%, 95% confidence interval [CI]: 1.9-21.4%) with uterine bleeding and large skin hemorrhage. Minor bleeding was observed in two patients (6.7%, 95% CI: 1.9-21.4%) presenting with nasal and gingival bleeding. Recanalization of the upper extremity deep veins was observed in all affected limbs at three months, and it persisted up to 6 months. The signs of upper limb post-thrombotic syndrome (PTS) were found in four patients (13.4%; 95% CI: 5.4-29.8%), and the mean modified Villalta score was 2.1 ±â€¯1.9. CONCLUSION: Treatment of UEDVT with rivaroxaban, preceded by one to two days of LMWH, seems to be safe and effective.


Assuntos
Anticoagulantes/uso terapêutico , Rivaroxabana/uso terapêutico , Trombose Venosa Profunda de Membros Superiores/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Adulto , Idoso , Anticoagulantes/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rivaroxabana/farmacologia
11.
Rev. bras. cir. plást ; 34(2): 268-273, apr.-jun. 2019. tab
Artigo em Inglês, Português | LILACS | ID: biblio-1015989

RESUMO

Introdução: Abdominoplastia consiste em um dos procedimentos estéticos mais populares realizados no Brasil. Pacientes pósbariátricos representam um desafio peculiar ao cirurgião plástico, uma vez que não só requerem reconstruções complexas, mas também apresentam comorbidades residuais e deficiências nutricionais. O tromboembolismo venoso (TEV) constitui uma complicação grave e potencialmente fatal da abdominoplastia. Apesar da pequena frequência desta complicação, os métodos aceitos como padrões para prevenção de TEV em pacientes após abdominoplastia, incluindo quimioprofilaxia, permanecem controversos. Objetivo: Avaliar a experiência do autor com rivaroxabana para profilaxia de TEV em pacientes submetidos a abdominoplastia após grande perda ponderal. Métodos: Uma série de 396 casos foi conduzida retrospectivamente. Todos os pacientes submetidos à abdominoplastia após cirurgia bariátrica que receberam rivaroxabana foram incluídos. A dose profilática foi de 10mg por dia. Dados demográficos, comorbidades, tipo de cirurgia e complicações foram registrados. Resultados: 396 casos de pacientes pós-bariátricos (356 mulheres e 40 homens) foram submetidos à abdominoplastia e receberam rivaroxabana no pós-operatório, de julho de 2015 a julho de 2018. A média de idade dos pacientes foi de 39,1 anos. O índice de massa corporal médio no momento da abdominoplastia foi de 27,2kg/m². Houve apenas um caso de tromboembolismo venoso (0,25%). Treze pacientes apresentaram hematoma com necessidade de drenagem. Conclusões: A quimioprofilaxia de rotina com rivaroxabana para pacientes submetidos à abdominoplastia após grande perda ponderal revela uma baixa incidência de TEV. Esta medicação oral é bem tolerada e apresenta um perfil de complicação aceitável.


Introduction: Abdominoplasty is one of the most popular aesthetic procedures performed in Brazil. Postbariatric patients present a challenge to the plastic surgeon as not only do they have complex reconstructive challenges but also they have residual medical comorbidities and nutritional deficiencies. A serious and potentially fatal complication of abdominoplasty is venous thromboembolism (VTE). Despite the frequency of this serious complication, the accepted standard methods to prevent VTE in abdominoplasty patients, including chemoprophylaxis, remain controversy. Objective: To evaluate the author experience with rivaroxaban, for VTE prophylaxis in abdominoplasty patients after massive weight loss. Methods: A retrospective 396 cases series were conducted. All patients who underwent abdominoplasty after bariatric surgery and received rivaroxaban were included. The prophylactic dose was 10 mg daily for 30 days, beginning 24 hours postoperatively. Patient demographics, comorbidities, type of surgery and complications were recorded. Results: From July 2015 until July 2018, 396 post bariatric patients (356 women and 40 men) underwent abdominoplasty and received rivaroxaban postoperatively. The mean body mass index prior to their weight loss procedure was 43.8kg/m2 (range, 37.3- 61.9kg/m2) and mean BMI was 27.2kg/m² at the time of the abdominoplasty. Mean patient age was 39.1 years. Only one patient had a symptomatic PTE event. Thirteen patients had a hematoma requiring operative evacuation, and all went on to heal without sequel. Conclusions: Routine chemoprophylaxis with rivaroxaban for abdominoplasty patients after massive weight loss has a low rate of VTE events. This oral medication is well tolerated and has an acceptable complication profile.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cirurgia Plástica/efeitos adversos , Cirurgia Plástica/métodos , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Trombose Venosa/cirurgia , Trombose Venosa/fisiopatologia , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Tromboembolia Venosa/cirurgia , Tromboembolia Venosa/complicações , Tromboembolia Venosa/fisiopatologia , Procedimentos Cirúrgicos Refrativos/métodos , Abdominoplastia/efeitos adversos , Abdominoplastia/métodos , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Rivaroxabana/farmacologia
12.
Eur J Clin Pharmacol ; 75(8): 1069-1075, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31139866

RESUMO

BACKGROUND: Routine laboratory monitoring of rivaroxaban and dose adjustment relating to exposure is currently not recommended. However, in certain clinical situations, assessment of rivaroxaban levels is desirable. OBJECTIVES: To examine inter- and intra-subject plasma rivaroxaban variability in patients with atrial fibrillation (AF) and to correlate these results to clinical outcomes. PATIENTS/METHODS: We included 60 patients with AF treated with rivaroxaban: half on 20 mg daily (R20) and half on 15 mg daily (R15). Three trough and peak blood samples were collected with an interval of 6-8 weeks apart. Plasma rivaroxaban concentration was measured directly by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and indirectly by anti-Xa for rivaroxaban, prothrombin time (PT), and activated partial thromboplastin time (APTT). RESULTS: Patients on R15 were older (76 ± 6 vs 71 ± 6 years), had lower creatinine clearance (60 ± 26 vs 99 ± 32 mL/min), higher CHADS2 (2.5 ± 1.2 vs 1.8 ± 1.3), all p < 0.01, but had similar rivaroxaban concentrations in trough samples to patients on R20. There was no significant intra-individual variability for trough or peak rivaroxaban concentration assessed by LC-MS/MS, anti-Xa, or PT. Trough rivaroxaban levels determined by LC-MS/MS (48 ± 30 vs 34 ± 26, p = 0.02) and anti-Xa, but not with PT and APTT, were higher in patients with bleeding than in patients without it. CONCLUSIONS: There is a pronounced inter-, but not intra-individual variability in the rivaroxaban trough levels in patients with AF. Assessment of trough rivaroxaban concentration with LC-MS/MS or anti-Xa, but not with APTT or PT, may help to identify patients at increased risk of bleeding.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Variação Biológica Individual , Variação Biológica da População , Inibidores do Fator Xa/farmacologia , Hemorragia/epidemiologia , Rivaroxabana/farmacologia , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea/estatística & dados numéricos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/estatística & dados numéricos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Medição de Risco , Rivaroxabana/uso terapêutico
13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(4): 468-473, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31109423

RESUMO

OBJECTIVE: To evaluate the effect and mechanism of rivaroxaban, an inhibitor of coagulation factor Xa (FXa), on endotoxin-induced injury to human umbilical vein endothelial cells (HUVEC). METHODS: When cultured HUVEC grow to 80% fusion, they were divided into four groups according to the random number method: blank control group (DMEM medium), lipopolysaccharide (LPS) group (cells were challenged by 100 µg/L LPS for 16 hours), FXa+LPS group (cells were challenged by LPS for 16 hours after they were cultured with 100 nmol/L FXa for 24 hours), and FXa +RIV+LPS group (cells were challenged by LPS for 16 hours after they were cultured with 100 nmol/L FXa and 1 µmol/L rivaroxaban for 24 hours). After each group of cells were challenged with LPS, the cell activity was detected by the cell proliferation and toxicity kit (CCK-8); the cell migration ability was detected by cell scratch experiments; the abilities of cells migration were measured by scratch-wound-healing assay; the apoptosis of cells were evaluated using flow cytometry; the endothelial barrier of cells was assessed by Transwell and Evans blue; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1ß, IL-6) were detected by the enzyme linked immunosorbent assay (ELISA); the expressions of nuclear factor-ΚB (NF-ΚB) and mitogen activated protein kinase (MAPK) signaling pathway were detected by Western Blot. RESULTS: Compared with blank control group, the cell viability in LPS group was significantly decreased, and the migration ability, number of apoptotic cells, and barrier permeability of endothelial cells was significantly increased, the levels of TNF-α, IL-1ß and IL-6 were significantly increased, and the expressions of phosphorylation of c-Jun N-terminal kinase (p-JNK), phosphorylation of p38MAPK (p-p38MAPK), phosphorylation of transforming growth factor kinase 1 (p-TAK1) and phosphorylation of NF-ΚBp65 (p-NF-ΚBp65) were significantly increased. It indicated that LPS could stimulate the inflammatory response of vascular endothelial cells, and had a significant impact on cell activity, apoptosis and function. There was no significant difference in above indexes between FXa+LPS group and LPS group, except for the level of IL-6 being higher in FXa+LPS group. Compared with FXa+LPS group, in FXa+RIV+LPS group, the cell activity was significantly increased (A value: 0.42±0.02 vs. 0.33±0.02), and migration ability was significantly decreased (folds: 1.78±0.17 vs. 2.24±0.20), the number of apoptotic cells was significantly decreased [(11.30±0.70)% vs. (21.03±0.19)%], and permeability of monolayers endothelial cells was significantly decreased [(149±12)% vs. (253±15)%], the levels of inflammatory cytokines were significantly decreased [IL-1ß (ng/L): 163.2±20.7 vs. 477.8±20.2, IL-6 (ng/L): 69.3±0.5 vs. 238.0±24.1, TNF-α (ng/L): 117.0±13.1 vs. 196.2±4.5], the expressions of p-TAK1 and p-NF-ΚBp65 were significantly decreased (p-TAK1/TAK1: 0.74±0.09 vs. 1.85±0.15, p-NF-ΚBp65/NF-ΚBp65: 1.15±0.17 vs. 2.36±0.20), with statistically significant differences (all P < 0.05). There was no significant difference in the p-JNK, p-p38MAPK expressions between FXa+RIV+LPS group and FXa+LPS group (p-JNK/JNK: 1.64±0.12 vs. 1.65±0.15, p-p38MAPK/p38MAPK: 2.31±0.32 vs. 2.35±0.20, both P > 0.05). CONCLUSIONS: Rivaroxaban can effectively relieve the inflammatory response of HUVEC stimulated by LPS, which may be related to the inhibition of NF-ΚB signaling pathway activation rather than MAPK signaling pathway.


Assuntos
Endotoxinas/efeitos adversos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Rivaroxabana/farmacologia , Humanos , Lipopolissacarídeos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
14.
Clin Appl Thromb Hemost ; 25: 1076029619847524, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31088146

RESUMO

The currently available oral anti-Xa agents are claimed to produce their anticoagulant and antithrombotic effects solely by the inhibition of factor Xa. This study profiled various anti-Xa drugs in routinely used laboratory assays to demonstrate that their effects are not solely related to the anti-Xa activities. Apixaban, betrixaban, edoxaban, and rivaroxaban were obtained commercially. Native and citrated whole blood was used for the activated clotting time (ACT) and thromboelastography (TEG). Citrated plasma was used for monitoring the prothrombin time (PT), activated partial thromboplastin time (aPTT), Heptest, and prothrombinase-induced clotting time (PiCT) tests. An amidolytic method was used for the determination of anti-Xa effects. Thrombin-induced fibrinokinetics was monitored optically. Thrombin generation studies were carried out using the calibrated automated thrombogram. All of the anti-Xa agents produced concentration- and assay-dependent effects. In the ACT at 2.5 µg/mL and TEG at 1.0 µg/mL, edoxaban exhibited the strongest anticoagulation effect. In the PiCT, PT, and aPTT assay at 1 µg/mL, edoxaban showed stronger effects than other agents. The half maximal inhibitory concentration of these agents for the inhibition of factor Xa ranged from 340 to >1000 ng/mL. In the thrombin generation inhibition assay, apixaban showed the strongest activity. In the fibrinokinetics, different anti-Xa agents produced varying degrees of inhibition. These results demonstrate that the measured anti-Xa activity alone does not fully reflect the overall biologic spectrum of these agents.


Assuntos
Benzamidas , Inibidores do Fator Xa , Fator Xa/metabolismo , Tempo de Protrombina , Pirazóis , Piridinas , Piridonas , Rivaroxabana , Benzamidas/farmacocinética , Benzamidas/farmacologia , Inibidores do Fator Xa/farmacocinética , Inibidores do Fator Xa/farmacologia , Humanos , Tempo de Tromboplastina Parcial , Pirazóis/farmacocinética , Pirazóis/farmacologia , Piridinas/farmacocinética , Piridinas/farmacologia , Piridonas/farmacocinética , Piridonas/farmacologia , Rivaroxabana/farmacocinética , Rivaroxabana/farmacologia , Tiazóis/farmacocinética , Tiazóis/farmacologia , Tromboelastografia
15.
Br J Biomed Sci ; 76(3): 122-128, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30967043

RESUMO

Background: The prothrombin time may be used to monitor the plasma concentration of rivaroxaban. However, there is variability in the responsiveness of rivaroxaban to different thromboplastins. We aimed to develop a rivaroxaban-monitoring method using the prothrombin time to reduce the differences in the sensitivity among reagents. Methods: Rivaroxaban-spiked pooled normal plasma at a 0-1000 ng/ml concentration was used to generate a rivaroxaban-adjusted sensitivity index (SI) values, and was tested with three thromboplastins. The warfarin-adjusted international sensitivity index (ISI-warfarin), rivaroxaban-adjusted sensitivity index (SI-rivaroxaban), international normalized ratio (INR) calculated with ISI-warfarin, normalized ratio (NR) calculated with SI-rivaroxaban, and their coefficient of variances (CVs) were compared. The NR-rivaroxaban value was compared with the results of an anti-Xa assay. Results: The ISI-warfarin and SI-rivaroxaban using different thromboplastins were 1.02 and 1.88, respectively, with Thromborel S, 0.90 and 1.00 using Recombiplastin 2G, and 1.30 and 1.15 using Neoplastin CI-plus. Between-thromboplastin variability expressed as CV were 6.3%-25.1% when expressed as INR-warfarin and 1.7%-4.7% when expressed as NR-rivaroxaban. CVs for the NR-rivaroxaban with another laboratory were significantly lower than those for INR-warfarin. Anti-Xa assay v NR-rivaroxaban correlation coefficients were 0.97-0.99. Conclusion: Using a rivaroxaban-specific NR effectively minimises inter-thromboplastin variability. By utilizing a NR-rivaroxaban, standardized prothrombin time results could be rapidly obtained, especially useful in standardizing the therapeutic effect of rivaroxaban.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/sangue , Coeficiente Internacional Normatizado , Tempo de Protrombina , Rivaroxabana/sangue , Tiofenos/sangue , Adulto , Inibidores do Fator Xa/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Reprodutibilidade dos Testes , Rivaroxabana/farmacologia , Tiofenos/farmacologia , Adulto Jovem
16.
J Atheroscler Thromb ; 26(10): 915-930, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30867376

RESUMO

AIM: A direct oral anti-coagulant, FXa inhibitor, has been applied to the clinical treatment of myocardial infarction (MI). Experimental studies in mice indicated that FXa inhibitors reduced atherosclerosis and prevented cardiac dysfunction after coronary ligation. These studies suggested that protease-activated receptor (PAR) 2, a major receptor of activated FX, may play an important role in atherosclerosis and cardiac remodeling. METHODS: The effects of a FXa inhibitor, rivaroxaban, were investigated in a new murine model of ischemic cardiomyopathy (ICM) using SR-BI KO/ApoeR61h/h mice (Hypo E mice) that developed MI by high-fat diet loading. RESULTS: Hypo E mice were fed rivaroxaban-containing (n=49) or control chow diets (n=126) after the induction of MI. The survival curve of the rivaroxaban-treated group 2 weeks after the induction of MI was improved significantly as compared with the non-treatment group (survival rate: 75.5% vs. 47.4%, respectively, p=0.0012). Echocardiography and the expression of BNP showed that rivaroxaban attenuated heart failure. Histological analyses revealed that rivaroxaban reduced aortic atherosclerosis and coronary occlusion, and markedly attenuated cardiac fibrosis. Rivaroxaban treatment decreased cardiac PAR2 levels and pro-inflammatory genes. In vitro, rivaroxaban application demonstrated the increase of cell viability against hypoxia in cardiac myocytes and the reduction of hypoxia-induced inflammation and fibrosis-related molecules in cardiac fibroblasts. The effects of the PAR2 antagonist against hypoxia-induced inflammation were comparable to rivaroxaban in cardiac fibroblasts. CONCLUSIONS: Rivaroxaban treatment just after MI in Hypo E mice prevented the progression of ICM by attenuating cardiac remodeling, partially through the suppression of the PAR2-mediated inflammatory pathway.


Assuntos
Cardiomiopatias/prevenção & controle , Dieta/efeitos adversos , Modelos Animais de Doenças , Inibidores do Fator Xa/farmacologia , Infarto do Miocárdio/complicações , Isquemia Miocárdica/prevenção & controle , Rivaroxabana/farmacologia , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Progressão da Doença , Masculino , Camundongos , Camundongos Knockout , Camundongos Knockout para ApoE , Infarto do Miocárdio/patologia , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/patologia , Receptores Depuradores Classe B/fisiologia
17.
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
18.
J Biochem Mol Toxicol ; 33(5): e22287, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719803

RESUMO

Activated factor X has a central role in the coagulation activation and also contributes to chronic inflammation and tissue fibrosis. In this study, rivaroxaban, a direct factor X inhibitor, attenuates liver fibrosis induced by carbon tetrachloride (CCl4 ). Male rats were randomly allocated into three groups: a control group, CCl 4 fibrotic group, and CCl 4 +rivaroxaban (5 mg/kg) group. Liver fibrosis was induced by subcutaneous injection of CCl 4 twice a week for 6 weeks. Rivaroxaban significantly restored the biochemical parameter including inflammatory and fibrosis markers with histopathological evidence using routine and Masson trichrome staining. It reduced also the expression of tissue factor, fibrin, transforming growth factor and α-smooth muscle actin in the liver tissues. This concludes that rivaroxaban attenuates liver injury caused by CCl 4 , at least in part by inhibiting coagulation and proinflammatory activation. In conclusion, rivaroxaban may be used for the management of liver fibrosis.


Assuntos
Intoxicação por Tetracloreto de Carbono/metabolismo , Inibidores do Fator Xa/farmacologia , Fator Xa/metabolismo , Cirrose Hepática/metabolismo , Rivaroxabana/farmacologia , Animais , Tetracloreto de Carbono/toxicidade , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Fator Xa/farmacologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Masculino , Ratos , Ratos Wistar
20.
Pathology ; 51(3): 292-300, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30665674

RESUMO

We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. LA is a marker of thrombophilia, and patients who have had a thrombosis may be placed on a DOAC. Thus, there is a high likelihood that LA testing will be requested on patients whilst they are on DOACs. In the current report, we have assessed data from our facility for the past two and a half years for all LA tests performed by RVVT testing, and have evaluated this data with respect to patient anticoagulant status. In total, there were 7170 test requests for RVVT associated testing during the period of data capture. Most LA-RVVT screen results (5008; ∼70%) were within normal limits, thereby excluding LA by RVVT method in most of the patient cohort. All DOACs led to a prolongation in both RVVT screen and confirm assays. However, rivaroxaban affected the screen more than the confirm, leading to higher RVVT ratios, whereas apixaban affected the confirm more than the screen, leading to lower RVVT ratios. LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.


Assuntos
Anticoagulantes/farmacologia , Síndrome Antifosfolipídica/diagnóstico , Testes de Coagulação Sanguínea , Coagulação Sanguínea/efeitos dos fármacos , Inibidor de Coagulação do Lúpus/análise , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/sangue , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Tempo de Protrombina , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Trombofilia/sangue , Trombofilia/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA