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2.
Ann Intern Med ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610549

RESUMO

Background: The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain. Objective: To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS. Design: 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36). Setting: 6 university hospitals in Spain. Participants: 190 adults (aged 18 to 75 years) with thrombotic APS. Intervention: Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis). Measurements: The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding. Results: After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease. Limitation: Anticoagulation intensity was not measured in the rivaroxaban group. Conclusion: Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis. Primary Funding Source: Bayer Hispania.

3.
Orphanet J Rare Dis ; 14(1): 196, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399146

RESUMO

BACKGROUND: Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE). METHODS: We used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT). RESULTS: Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE. CONCLUSIONS: During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis.

4.
Eur J Intern Med ; 68: 30-35, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31427187

RESUMO

BACKGROUND: The clinical outcomes during the course of anticoagulation in patients with venous thromboembolism (VTE) using statins remain controversial. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the risk for VTE recurrences, major bleeding or death during anticoagulation, according to the use of statins at baseline. We used propensity score-matching (PSM) to adjust for confounding variables. RESULTS: From February 2009 to January 2018, 32,062 VTE patients were included. Of these, 7,085 (22%) were using statins. Statin users were 10 years older (73±11 vs. 63±19 years, respectively) and more likely to have comorbidities or to be using antiplatelets or corticosteroids at baseline than non-users. During the course of anticoagulation (median, 177 days), 694 patients developed VTE recurrences, 848 bled and 3,169 died (fatal pulmonary embolism 176, fatal bleeding 121). Statin users had a similar rate of VTE recurrences (hazard ratio [HR]: 0.98; 95%CI: 0.82-1.17), a higher rate of major bleeding (HR: 1.29; 95%CI: 1.11-1.50) and a similar mortality rate (HR: 1.01; 95%CI: 0.93-1.10) than non-users. On PSM analysis, statin users had a significantly lower risk for death (HR: 0.62; 95%CI: 0.48-0.79) and a similar risk for VTE recurrences (HR: 0.98; 95%CI: 0.61-1.57) or major bleeding (HR: 0.85; 95%CI: 0.59-1.21) than non-users. CONCLUSIONS: During anticoagulation for VTE, patients using statins at baseline had a lower risk to die than non-users.

5.
Cells ; 8(9)2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450639

RESUMO

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT.

6.
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
7.
J Thromb Haemost ; 17(8): 1217-1228, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31063646

RESUMO

Essentials Debated is the role of residual pulmonary obstruction (RPO) in predicting venous thromboembolism. Whether right ventricular dysfunction (RVD) predicts recurrent venous thromboembolism is unknown. 15 studies on RPO and 4 on RVD and venous thromboembolism were included in this meta-analysis. RPO is a predictor of recurrent venous thromboembolism when assessed by perfusion lung scan. RVD after acute pulmonary embolism is not associated with recurrent venous thromboembolism. BACKGROUND: There is conflicting evidence regarding the role of residual pulmonary obstruction (RPO) or persistent right ventricular dysfunction (RVD) after pulmonary embolism (PE) as a predictor of recurrent venous thromboembolism (VTE). The aim of this study was to assess whether RPO or persistent RVD after PE is associated with recurrent VTE. METHODS: MEDLINE and EMBASE were searched through December 2018. Studies reporting on (a) RPO either on computed tomography (CT) angiography or perfusion lung scan, or RVD on echocardiography or CT angiography, after therapeutic anticoagulation for the acute PE, and (b) recurrent VTE, were included in this meta-analysis. RESULTS: RPO was associated with an increased risk of recurrent VTE (16 studies; 3472 patients; odds ratio [OR] 2.22; 95% confidence interval [CI] 1.61-3.05; I2  = 26%); the association was statistically significant for lung scan-detected RPO (11 studies; 2916 patients; OR 2.21; 95% CI 1.63-3.01) but not for CT angiography-detected RPO (five studies; 556 patients; OR 2.56; 95% CI 0.82-7.94). No significant association was found between persistent RVD and recurrent VTE (four studies; 852 patients; OR 1.62; 95% CI 0.63-4.17). CONCLUSIONS: RPO is a predictor of recurrent VTE after a first acute PE, mainly when assessed by perfusion lung scan.

8.
Med. clín (Ed. impr.) ; 152(7): 274-280, abr. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183547

RESUMO

La telangiectasia hemorrágica hereditaria es una enfermedad minoritaria con herencia autosómica dominante que ocasiona un crecimiento vascular anómalo de forma sistémica. El abordaje y seguimiento de estos pacientes debería hacerse desde unidades multidisciplinares. Su diagnóstico es clínico según los criterios de Curaçao. Las telangiectasias en la mucosa nasal ocasionan epistaxis recurrentes, principal síntoma de esta enfermedad y de difícil control. Los 3 patrones de afectación hepática, comunicaciones entre arteria hepática y venas suprahepáticas, entre arteria hepática y vena porta o entre vena porta y venas suprahepáticas pueden causar insuficiencia cardiaca por hiperaflujo, hipertensión portal o encefalopatía hepática, respectivamente. Estos tipos de afectación vascular se pueden establecer mediante tomografía computarizada. Se debe realizar un cribado de fístulas arteriovenosas pulmonares a todos los pacientes mediante una ecocardiografía con contraste. Nuestro principal objetivo es realizar una revisión del manejo de las epistaxis, afectación hepática y pulmonar del paciente adulto con telangiectasia hemorrágica hereditaria


Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant inherited Rare Disease that causes a systemic anomalous vascular overgrowth. The approach and follow-up of these patients should be from multidisciplinary units. Its diagnosis is carried out according to Curaçao clinical Criteria. Telangiectasia in the nasal mucosa cause recurrent epistaxis, the main symptom of HHT and difficult to control. The three types of hepatic shunting, hepatic artery to hepatic vein, hepatic artery to portal vein or to portal vein to hepatic vein, can cause high-output heart failure, portal hypertension or porto-systemic encephalopathy, respectively. These types of vascular involvement can be established using computerised tomography. Pulmonary arteriovenous fistula should be screened for all HHT patients by contrast echocardiography. The main objective is to review the management of epistaxis, liver and lung involvement of the adult patient with HHT


Assuntos
Humanos , Adulto , Telangiectasia Hemorrágica Hereditária/terapia , Epistaxe/terapia , Fístula do Sistema Respiratório/terapia , Fístula Arteriovenosa/terapia , Telangiectasia Hemorrágica Hereditária/complicações , Epistaxe/etiologia , Fístula do Sistema Respiratório/etiologia , Fístula Arteriovenosa/etiologia
9.
Med Clin (Barc) ; 152(7): 274-280, 2019 04 05.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30502301

RESUMO

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant inherited Rare Disease that causes a systemic anomalous vascular overgrowth. The approach and follow-up of these patients should be from multidisciplinary units. Its diagnosis is carried out according to Curaçao clinical Criteria. Telangiectasia in the nasal mucosa cause recurrent epistaxis, the main symptom of HHT and difficult to control. The three types of hepatic shunting, hepatic artery to hepatic vein, hepatic artery to portal vein or to portal vein to hepatic vein, can cause high-output heart failure, portal hypertension or porto-systemic encephalopathy, respectively. These types of vascular involvement can be established using computerised tomography. Pulmonary arteriovenous fistula should be screened for all HHT patients by contrast echocardiography. The main objective is to review the management of epistaxis, liver and lung involvement of the adult patient with HHT.

11.
Arterioscler Thromb Vasc Biol ; 38(5): 1216-1229, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29449337

RESUMO

OBJECTIVE: ALK1 (activin-receptor like kinase 1) is an endothelial cell-restricted receptor with high affinity for BMP (bone morphogenetic protein) 9 TGF-ß (transforming growth factor-ß) family member. Loss-of-function mutations in ALK1 cause a subtype of hereditary hemorrhagic telangiectasia-a rare disease characterized by vasculature malformations. Therapeutic strategies are aimed at reducing potential complications because of vascular malformations, but currently, there is no curative treatment for hereditary hemorrhagic telangiectasia. APPROACH AND RESULTS: In this work, we report that a reduction in ALK1 gene dosage (heterozygous ALK1+/- mice) results in enhanced retinal endothelial cell proliferation and vascular hyperplasia at the sprouting front. We found that BMP9/ALK1 represses VEGF (vascular endothelial growth factor)-mediated PI3K (phosphatidylinositol 3-kinase) by promoting the activity of the PTEN (phosphatase and tensin homolog). Consequently, loss of ALK1 function in endothelial cells results in increased activity of the PI3K pathway. These results were confirmed in cutaneous telangiectasia biopsies of patients with hereditary hemorrhagic telangiectasia 2, in which we also detected an increase in endothelial cell proliferation linked to an increase on the PI3K pathway. In mice, genetic and pharmacological inhibition of PI3K is sufficient to abolish the vascular hyperplasia of ALK1+/- retinas and in turn normalize the vasculature. CONCLUSIONS: Overall, our results indicate that the BMP9/ALK1 hub critically mediates vascular quiescence by limiting PI3K signaling and suggest that PI3K inhibitors could be used as novel therapeutic agents to treat hereditary hemorrhagic telangiectasia.


Assuntos
Receptores de Activinas Tipo II/genética , Receptores de Ativinas Tipo I/genética , Células Endoteliais/enzimologia , Mutação , Neovascularização Patológica , Fosfatidilinositol 3-Quinase/metabolismo , Telangiectasia Retiniana/genética , Telangiectasia Hemorrágica Hereditária/genética , Receptores de Ativinas Tipo I/deficiência , Inibidores da Angiogênese/farmacologia , Animais , Estudos de Casos e Controles , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Ativação Enzimática , Deleção de Genes , Predisposição Genética para Doença , Fator 2 de Diferenciação de Crescimento/farmacologia , Células Endoteliais da Veia Umbilical Humana/enzimologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Hiperplasia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Inibidores de Proteínas Quinases/farmacologia , Telangiectasia Retiniana/tratamento farmacológico , Telangiectasia Retiniana/enzimologia , Telangiectasia Retiniana/patologia , Transdução de Sinais , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/enzimologia , Telangiectasia Hemorrágica Hereditária/patologia , Fator A de Crescimento do Endotélio Vascular/farmacologia
12.
Semin Thromb Hemost ; 44(4): 341-347, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29329472

RESUMO

Small studies have suggested differences in demographics and outcomes between left- and right-sided deep vein thrombosis (DVT), and also unilateral versus bilateral DVT. We investigated the clinical presentation and outcomes of patients with DVT based on thrombus sidedness. The authors used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) database (2001-2016) to identify patients with symptomatic proximal lower-extremity DVT. Main outcomes included cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality. Overall, 30,445 patients were included. The majority of DVTs occurred in the left leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; p < 0.001 for chi-squared test comparing all three groups). Comorbidities were relatively similar in those with left-sided and right-sided DVT. Compared with those with left-sided DVT, patients with right-sided DVT had higher relative frequency of PE (26% versus 23%, p < 0.001) and 1-year mortality (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.00-1.18). This difference in mortality did not persist after multivariable adjustment (OR: 1.01; 95% CI: 0.93-1.1). Patients with bilateral DVT had a greater burden of comorbidities such as heart failure, and recent surgery compared with those with unilateral DVT (p < 0.001), and higher relative frequency of PE (48%), and 1-year mortality (24.1%). Worse outcomes in patients with bilateral DVT were attenuated but persisted after multivariable adjustment for demographics and risk factors (OR: 1.64; 95% CI: 1.43-1.87). Patients with bilateral DVT had worse outcomes during and after discontinuation of anticoagulation. There is a left-sided preponderance for proximal lower-extremity DVT. Compared with those with left-sided DVT, patients with right-sided DVT have slightly higher rates of PE. Bilateral DVT is associated with markedly worse short-term and 1-year outcomes.


Assuntos
Anticoagulantes/administração & dosagem , Sistema de Registros , Trombose Venosa , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Trombose Venosa/tratamento farmacológico , Trombose Venosa/mortalidade , Trombose Venosa/patologia
13.
Thromb Res ; 151 Suppl 1: S11-S15, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28262227

RESUMO

BACKGROUND: In patients with venous thromboembolism (VTE) and factor V Leiden (FVL) or prothrombin 20210G-A mutation (PTM), the influence of gender on outcome has not been consistently studied. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to assess the existence of gender differences in the rate of VTE recurrences (deep vein thrombosis [DVT] or pulmonary embolism [PE]) or major bleeding during the course of anticoagulation and after its discontinuation in FVL and PTM carriers. RESULTS: From March 2001 to September 2016, 11,224 VTE patients underwent thrombophilia testing. Of these, 1,563 were FVL carriers (863 men and 700 women) and 1,231 were PTM carriers (659 men and 572 women). During the course of anticoagulant therapy, men with FVL had a 6-fold higher rate of VTE recurrences than major bleeds (31 vs. 5 events). In women with FVL, the rate of VTE recurrences was 2-fold higher (16 vs. 8), as was in men (17 vs. 8) or women (17 vs. 9) with PTM. After discontinuing anticoagulation, men with FVL had a 3-fold higher rate of DVT recurrences than women (hazard ratio [HR]: 3.13; 95% CI: 1.79-5.67), with no differences in PE recurrences. Among patients with PTM, there were no gender differences in the rate of DVT (HR: 1.89; 95% CI: 1.00-3.65) or PE recurrences (HR: 1.82; 95% CI: 0.83-4.12). CONCLUSIONS: During the anticoagulation course, men with FVL are at a much higher risk for VTE recurrences than bleeding. After discontinuing anticoagulation, men with FVL are at an increased risk for DVT recurrences.


Assuntos
Anticoagulantes/uso terapêutico , Fator V/genética , Protrombina/genética , Trombofilia/tratamento farmacológico , Trombofilia/epidemiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Fatores Sexuais , Trombofilia/genética , Trombofilia/patologia , Resultado do Tratamento , Tromboembolia Venosa/genética , Tromboembolia Venosa/patologia
14.
Eur J Intern Med ; 36: 62-66, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27495947

RESUMO

BACKGROUND: The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain. METHODS: We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years. RESULTS: Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported. CONCLUSIONS: Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.


Assuntos
Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Embolia Pulmonar/tratamento farmacológico , Sistema de Registros , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Comorbidade , Feminino , Insuficiência Cardíaca/epidemiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Embolia Pulmonar/epidemiologia , Recidiva , Insuficiência Renal/epidemiologia , Espanha/epidemiologia , Resultado do Tratamento , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Varfarina/uso terapêutico
15.
Thromb Haemost ; 116(4): 739-46, 2016 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-27535349

RESUMO

The pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deep-vein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox proportional hazards model. Analyses were performed for both the first 21 days of treatment and the whole treatment period. For rivaroxaban recipients, there was no association between bodyweight or body mass index (BMI) and risk of recurrent VTE (ptrend=0.87 and 0.62, respectively), major bleeding (ptrend=0.24 and 0.36, respectively) or clinically relevant bleeding (ptrend=0.17 and 0.63, respectively). Major bleeding events were numerically lower in rivaroxaban patients across all bodyweight and BMI categories. Hazard ratios for rivaroxaban vs enoxaparin/VKA were similar in all bodyweight and BMI categories, both during the first 21 days and the whole treatment period. The fixed-dose rivaroxaban regimen is not associated with an increased risk of major bleeding or recurrent VTE in patients with either a low or high bodyweight. A high BMI was not associated with an increased risk of recurrent VTE during anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Peso Corporal , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Enoxaparina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Rivaroxabana/administração & dosagem , Vitamina K/antagonistas & inibidores , Adulto Jovem
16.
Ann Am Thorac Soc ; 12(8): 1122-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26114586

RESUMO

RATIONALE: Patients with acute symptomatic pulmonary embolism (PE) deemed to be at low risk for early complications might be candidates for partial or complete outpatient treatment. OBJECTIVES: To develop and validate a clinical prediction rule that accurately identifies patients with PE and low risk of short-term complications and to compare its prognostic ability with two previously validated models (i.e., the Pulmonary Embolism Severity Index [PESI] and the Simplified PESI [sPESI]) METHODS: Multivariable logistic regression of a large international cohort of patients with PE prospectively enrolled in the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry. MEASUREMENTS AND MAIN RESULTS: All-cause mortality, recurrent PE, and major bleeding up to 10 days after PE diagnosis were determined. Of 18,707 eligible patients with acute symptomatic PE, 46 (0.25%) developed recurrent PE, 203 (1.09%) bled, and 471 (2.51%) died. Predictors included in the final model were chronic heart failure, recent immobilization, recent major bleeding, cancer, hypotension, tachycardia, hypoxemia, renal insufficiency, and abnormal platelet count. The area under receiver-operating characteristic curve was 0.77 (95% confidence interval [CI], 0.75-0.78) for the RIETE score, 0.72 (95% CI, 0.70-0.73) for PESI (P < 0.05), and 0.71 (95% CI, 0.69-0.73) for sPESI (P < 0.05). Our RIETE score outperformed the prognostic value of PESI in terms of net reclassification improvement (P < 0.001), integrated discrimination improvement (P < 0.001), and sPESI (net reclassification improvement, P < 0.001; integrated discrimination improvement, P < 0.001). CONCLUSIONS: We built a new score, based on widely available variables, that can be used to identify patients with PE at low risk of short-term complications, assisting in triage and potentially shortening duration of hospital stay.


Assuntos
Anticoagulantes/uso terapêutico , Pacientes Ambulatoriais/estatística & dados numéricos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/terapia , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Técnicas de Apoio para a Decisão , Feminino , Hemorragia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Curva ROC , Sistema de Registros , Medição de Risco
19.
Thromb Res ; 134(6): 1265-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25457585

RESUMO

INTRODUCTION: The role of thrombolysis in hemodynamically stable patients with acute pulmonary embolism (PE) remains controversial. We performed a meta-analysis of randomized trials to assess the effect of thrombolysis in these patients. MATERIALS AND METHODS: We searched MEDLINE and EMBASE for randomized studies comparing thrombolysis and heparin for the initial treatment of hemodynamically stable PE patients. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated. NNH to cause a major bleeding (MB) or an intracranial hemorrhage (ICH) and NNT to avoid one death were also calculated. RESULTS: Eleven studies (1833 patients) were included seven with rt-PA, three with tenecteplase and one with urokinase. Patients randomized to thrombolysis had a significant increased risk for MB (5.9% vs 1.9%; OR 2.83, 95% CI 1.68-4.76, I2 18.7%) and an increased risk for ICH (1.74% versus 0.6%; OR 2.36, 95% CI 0.98-5.71, I2 0%) and for fatal bleeding (1.3% versus 0.54%; OR 1.84, 95% CI 0.73-4.61, I2 0%). A not-significant reduction for all-cause death (1.74% vs 2.51%; OR 0.68, 95% CI 0.37-1.26, I2 0%) and a significant reduction for recurrent PE (1.1% vs 2.5%; OR 0.44, 95% CI 0.21-0.92, I2 0%) in favor of thrombolysis compared with heparin was found. NNH to cause a MB or an ICH were 27 and 91 patients, respectively. NNT to avoid one death was 125 patients. CONCLUSIONS: Due to increased risk for MB and ICH with no evidence of reduction in mortality, thrombolysis should not be used for most normotensive PE patients.


Assuntos
Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Hemorragias Intracranianas/mortalidade , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/mortalidade , Terapia Trombolítica/mortalidade , Doença Aguda , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causalidade , Feminino , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/mortalidade , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
20.
Arch Bronconeumol ; 49(12): 534-47, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24041726
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