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1.
Chest ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34627853

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated venous thromboembolism (VTE). RESEARCH QUESTION: Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE? STUDY DESIGN AND METHODS: In a randomized open-label non-inferiority trial, patients with active cancer who had proximal deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) were randomly assigned to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months. RESULTS: Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence 6.4% vs 10.1%, subdistribution hazard ratio [SHR] 0.75, 95% confidence interval [CI] 0.21-2.66, in both the intention-to-treat and per-protocol populations). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence 1.4% vs 3.7%, SHR 0.36, 95%CI 0.04-3.43). Major or clinically relevant non-major bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence 12.2% vs 9.8%, SHR 1.27, 95%CI 0.49-3.26). Overall, 19 (25.7%) and 20 (23.8%) patients died in the rivaroxaban and dalteparin groups, respectively (HR 1.05, 95% CI, 0.56-1.97). INTERPRETATION: In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for non-inferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided. TRIAL REGISTRATION: NCT02746185.

3.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360659

RESUMO

Platelets are hematopoietic cells whose main function has for a long time been considered to be the maintenance of vascular integrity. They have an essential role in the hemostatic response, but they also have functional capabilities that go far beyond it. This review will provide an overview of platelet functions. Indeed, stress signals may induce platelet apoptosis through proapoptotis or hemostasis receptors, necrosis, and even autophagy. Platelets also interact with immune cells and modulate immune responses in terms of activation, maturation, recruitment and cytokine secretion. This review will also show that platelets, thanks to their wide range of innate immune receptors, and in particular toll-like receptors, and can be considered sentinels actively participating in the immuno-surveillance of the body. We will discuss the diversity of platelet responses following the engagement of these receptors as well as the signaling pathways involved. Finally, we will show that while platelets contribute significantly, via their TLRs, to immune response and inflammation, these receptors also participate in the pathophysiological processes associated with various pathogens and diseases, including cancer and atherosclerosis.


Assuntos
Aterosclerose/patologia , Plaquetas/patologia , Imunidade Inata/imunologia , Neoplasias/patologia , Ativação Plaquetária , Receptores Imunológicos/metabolismo , Receptores Toll-Like/metabolismo , Animais , Aterosclerose/imunologia , Aterosclerose/metabolismo , Plaquetas/imunologia , Plaquetas/metabolismo , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo
4.
Vascul Pharmacol ; 139: 106883, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34091065

RESUMO

The outbreak of 2019 novel coronavirus disease (Covid-19) has deeply challenged the world population, but also our medical knowledge. Special attention has been paid early to an activation of coagulation, then to an elevated rate of venous thromboembolism (VTE) in patients hospitalized with severe COVID-19. These data suggested that anticoagulant drugs should be evaluated in the treatment of patients with COVID-19. The publication of unexpected high rates of VTE in patients hospitalized with COVID-19, despite receiving thromboprophylaxis, open the way to dedicated trials, evaluating modified regimens of thromboprophylaxis. Moreover, the further improvement in our comprehension of the disease, particularly the pulmonary endothelial dysfunction increased the hope that anticoagulant drugs may also protect patients from pulmonary thrombosis. In this comprehensive review, we cover the different situations where thromboprophylaxis standard may be modified (medically-ill inpatients, ICU inpatients, outpatients), and describe some of the current randomized controls trials evaluating new regimens of thromboprophylaxis in patients with COVID-19, including the preliminary available results. We also discuss the potential of anticoagulant drugs to target the thromboinflammation described in patients with severe COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/tratamento farmacológico , Embolia Pulmonar/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Humanos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidade , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/mortalidade
6.
Ther Drug Monit ; 43(4): 455-458, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33908408

RESUMO

ABSTRACT: In this article, we present a case of apixaban elimination prolonged by 450% in a patient with coronavirus disease 2019 because of multiple conditions, including drug-drug interaction, severe inflammation, and acute kidney injury. Therapeutic drug monitoring was used to explain unusual routine coagulation assays. This grand round highlights the importance of dialog between the clinician and a therapeutic drug monitoring consultant for optimal patient care.


Assuntos
Injúria Renal Aguda/metabolismo , COVID-19/metabolismo , Monitoramento de Medicamentos/métodos , Pirazóis/metabolismo , Piridonas/metabolismo , Eliminação Renal/efeitos dos fármacos , Visitas com Preceptor/métodos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Antivirais/metabolismo , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Interações Medicamentosas/fisiologia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/metabolismo , Inibidores do Fator Xa/uso terapêutico , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/prevenção & controle , Masculino , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Eliminação Renal/fisiologia , Índice de Gravidade de Doença , Fatores de Tempo
7.
J Thromb Haemost ; 19(5): 1299-1306, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33660901

RESUMO

BACKGROUND: Meta-analyses are widely used to strengthen available evidence and obtain more precise estimates of treatment effect than any individual trial. Paradoxically, multiplication of meta-analyses on the same topic can lead to confusion as practitioners no longer benefit from a rapid and synthetic response. This phenomenon may appear disproportionate when the number of published meta-analyses exceeds the number of original studies. OBJECTIVES: To describe an example of redundant meta-analyses published in the same area with the same randomized clinical trials (RCTs). METHODS: A systematic review was performed to identify all published meta-analyses of original RCTs that compared direct oral anticoagulants with low molecular weight heparins in cancer patients with venous thromboembolism (VTE). Forest plots were used to represent the meta-analyses results for efficacy (VTE recurrence) and safety (major bleeding) endpoints. An authors' network was constructed to explore the links between the authors of the published meta-analyses. RESULTS: In the past 3 years, four original RCTs were the subject of 20 published meta-analyses by 142 authors: five, four, and 11 meta-analyses pooled the data of two, three, and four RCTs, respectively. The results of meta-analyses were similar regarding the risks of VTE recurrence and major bleeding. The 11 meta-analyses of four RCTs were published within 6 months of the publication of the last RCT. CONCLUSIONS: The epidemic proportions of such redundant literature and authorship could be moderated by developing "living" meta-analyses and encouraging authors of new RCTs to update the corresponding meta-analysis in the same paper as their original research.


Assuntos
Epidemias , Metanálise como Assunto , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Heparina de Baixo Peso Molecular , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia
8.
Hamostaseologie ; 41(2): 128-135, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33711849

RESUMO

Aside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage. With these types of stress, they undergo morphologic, metabolic, and functional modulations which are likely to induce platelet activation and the release of biological response modifiers (BRMs). As a consequence, platelet concentrates (PCs) accumulate BRMs during processing and storage, and these BRMs are ultimately transfused alongside platelets. It has been shown that BRMs present in PCs can induce immune responses and posttransfusion reactions in the transfusion recipient. Several recent reports within the transfusion literature have investigated the concept of platelets as immune cells. Nevertheless, current and future investigations will face the challenge of encompassing the immunological role of platelets in the scope of transfusion.

10.
J Cancer Res Clin Oncol ; 147(11): 3447-3454, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33715087

RESUMO

BACKGROUND: There are still controversial data regarding the prognostic value of Venous ThromboEmbolism (VTE) in advanced Pancreatic Ductal AdenoCarcinoma (PDAC) and thromboprophylaxis is poorly prescribed despite international recommendations. METHODS: Medical charts of patients consecutively treated for advanced PDAC from 2010 to 2019 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Prognostic Factors were identified using a multivariate Cox's proportional hazard model. Early VTE was defined as VTE occurring within the three months following the PDAC diagnosis. RESULTS: A total of 174 patients were included (median age: 67 years; males: 55.2%; performance status (PS) 0-1: 88.5%) with metastatic disease in 74.7%. At baseline, Khorana score was high (≥ 3) in the vast majority of cases (93.7%). The cumulative incidences of VTE were 12.4% (95% CI 7.3-17.2) at 3 months, 20.4% (95% CI 13.9-26.4) at 6 months and 28.1% (95% CI 20.0-35.3) at 12 months. Patients who experienced early VTE had shorter PFS (3.8 months vs. 7.1 months; HR = 2.02; 95% CI 1.21-3.37; p = 0.006) and shorter OS (8.0 months vs. 14.1 months; HR = 2.42; 95% CI 1.37-4.30; p = 0.002) compared to the others, independently of prognostic factors such as PS, liver metastases, carcinomatosis, and chemotherapy regimen. CONCLUSION: early VTE is a strong prognostic factor in advanced PDAC and occurs in about one in 10 patients.

12.
JAMA ; 325(1): 59-68, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399840

RESUMO

Importance: The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain. Objective: To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms. Design, Setting, and Participants: Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017. Exposures: Acutely worsening respiratory symptoms in patients with COPD. Main Outcomes and Measures: The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not. Results: Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441). Conclusions and Relevance: Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.


Assuntos
Algoritmos , Doença Pulmonar Obstrutiva Crônica/complicações , Embolia Pulmonar/diagnóstico , Idoso , Estudos Transversais , Feminino , Seguimentos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Prevalência , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Trombose Venosa/etiologia
13.
Thromb Res ; 198: 40-48, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278785

RESUMO

INTRODUCTION: Methods for prognosis assessment and patient management in acute pulmonary embolism (PE) are much debated among physicians. We conducted an online survey to determine physician's attitudes and barriers towards the use of prognostic models when treating patients with acute PE. METHOD: Physicians members of the French and the European scientific societies for emergency medicine or of a French thrombosis research network were reached by their respective scientific societies and invited to participate via email. The questionnaire was a mixture of close-ended with yes-no or multiple-choice options and a small number of open-ended questions. RESULTS: The survey included 461 respondents. The most commonly used prognostic tools were clinical judgment (36%) and prognostic models (29.5%). Prognostic models were used by 57% of respondents in more than half of all cases and prognostic indicators by 62% in addition to prognostic models. Affiliation group and type of hospital emerged as independent predictors for choosing prognostic models. Many (52%) reported lack of familiarity with the models and reported clinical judgment (60%) or hospital checklists (73%) as being as good as or better than prognostic models. The highest acceptable 30-day mortality rate limit for early discharge or outpatient management was deemed to be 1%, but few patients are discharged early or completely managed on an outpatient basis. CONCLUSIONS: This survey provides new information for implementing knowledge translation strategies to improve prognostic risk assessment for acute PE patients, and highlights the need for considering the use of clinical judgment and hospital checklists in future clinical research.


Assuntos
Embolia Pulmonar , Doença Aguda , Atitude , Humanos , Prognóstico , Embolia Pulmonar/diagnóstico , Medição de Risco , Inquéritos e Questionários
14.
J Clin Epidemiol ; 130: 49-58, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33080342

RESUMO

BACKGROUND AND OBJECTIVES: Randomized controlled trials (RCTs) are criticized for including patients who are overselected. Health authorities consequently encourage "real-world" postmarketing cohort studies. Our objective was to determine the differences between RCTs and observational studies as regards their populations and efficacy/safety results. METHODS: A systematic review was conducted to identify RCTs and observational studies including patients with venous thromboembolism receiving direct oral anticoagulants or conventional treatment. Ratios of hazard ratio (RHR) comparing epidemiological studies (prospective and retrospective cohort studies and studies using living databases) with RCTs were computed. RESULTS: Six RCTs (27,121 patients) and twenty observational studies (248,971 patients) were identified and analyzed. Prospective cohort studies seemed to recruit patients who were no less selected than those of RCTs whereas other types of observational studies may reflect the population treated in real life. Among observational studies, prospective cohort studies yielded the most favorable estimates of treatment effect compared with RCTs. These studies were associated with a nonsignificant 33% increase in efficacy estimate (RHR 0.67, [95% CI, 0.39-1.18]) but no effect on safety estimate. Studies using living databases were associated with nonsignificant trends toward a greater effect on efficacy (RHR 0.82, [0.66-1.01]) and a smaller effect on safety (RHR 1.33, [0.96-1.84]). DISCUSSION: Overall, in this clinical setting, an exaggeration of the treatment efficacy estimate was seen with observational studies compared with RCTs. CONCLUSIONS: As the presence of residual confounding cannot be excluded, these results should be interpreted cautiously.

15.
Sci Rep ; 10(1): 15415, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963332

RESUMO

The aim of this study was to propose a methodology for the assessment of non-inferiority with meta-analysis. Assessment of hypofractionated RT in prostate and breast cancers is used as an illustrative example. Non-inferiority assessment of an experimental treatment versus an active comparator should rely on two elements: (1) an estimation of experimental treatment's effect versus the active comparator based on a meta-analysis of randomized controlled trials and (2) the value of an objective non-inferiority margin. This margin can be defined using the reported effect of active comparator and the percentage of the active comparator's effect that is desired to be preserved. Non-inferiority can then be assessed by comparing the upper bound of the 95% confidence interval of experimental treatment's effect to the value of the objective non-inferiority margin. Application to hypofractionated RT in breast cancer showed that hypofractionated whole breast irradiation (HWBI) appeared to be non-inferior to conventionally fractionated RT for local recurrence. This was not the case for accelerated partial breast irradiation (APBI). Concerning overall survival, non-inferiority could not be claimed for either HWBI or APBI. For prostate cancer, the lack of demonstrated significant superiority of conventional RT versus no RT precluded any conclusion regarding non-inferiority of hypofractionated RT.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Próstata/radioterapia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/radioterapia , Hipofracionamento da Dose de Radiação , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Artigo em Inglês | MEDLINE | ID: mdl-32543165

RESUMO

BACKGROUND: Vascular calcification is an established feature of atherosclerosis process. The sodium/phosphate transporter PiT-1 acts as a biosensor in vascular calcification of VSMCs. [99mTc]-Pentavalent dimercaptosuccinic acid (99mTc-(V)-DMSA) was mediated by PiT-1 transporter in tumoral cells and we propose its evaluation in a vascular calcification in vitro model. The aim of this study was to determine if 99mTc-(V)-DMSA can follow the vascular calcification process in vascular smooth muscle cells (VSMCs) based on PiT-1 expression. METHODS: From a rat aortic VSMC cell line (A7r5), we set up a model of calcification within 7 days using a calcifying medium containing a high inorganic phosphate concentration. Phosphocalcic deposits were monitored with Alizarin red and Von Kossa staining and with phase contrast microscopy. PiT-1 expression was evaluated with an immunofluorescence assay and osteopontin expression, with whole cell ELISA assay. 99mTc-(V)-DMSA uptake was measured in control and calcifying conditions and compared with optical microscopy evaluation. RESULTS: Under hyperphosphatemia conditions, the VSMC cells progressively overexpressed osteopontin protein, PiT-1 transporter, and synthetized mineralized matrix with phosphocalcic deposition. 99mTc-(V)-DMSA uptake was to 2.8+/-2.08%DA/mg-protein in control cells and 42+/-24%DA/mg-protein in calcified cells (p<0,001). PiT-1 inhibition with phosphonoformic acid completely reverse the calcium deposition as well as the 99mTc-(V)- DMSA uptake. These results demonstrated that 99mTc-(V)-DMSA in vitro uptake is mediated by PiT-1 transporter and follow the VSMC calcification process. CONCLUSIONS: These preliminary in vitro results showed 99mTc-(V)-DMSA uptake follow the phospho-calcic deposition mediated by PiT-1 transporter. This radiotracer may have some potential to detect changes of VSMC metabolism occurring in the atherosclerosis process.

17.
J Clin Epidemiol ; 124: 24-33, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32298778

RESUMO

OBJECTIVES: An unexpected promising effect of low molecular weight heparins (LMWHs) on survival in patients with cancer was observed in early trials in post hoc subgroup analyses but not found in more recent trials. To highlight a possible regression over time toward the lack of the antitumoral effect of LMWHs, we performed a cumulative meta-analysis of survival data from randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: Medical databases were searched to identify RCTs comparing, in patients with cancer, LMWHs with placebo or no treatment in patients free of venous thromboembolism (VTE), or to vitamin K antagonists in patients who experienced an acute VTE in overall survival. The cumulative hazard ratio (HR) was estimated after each study inclusion in chronological order. RESULTS: Twenty-three studies (12,970 patients) were included. The cumulative meta-analysis of the earlier trials showed a significant improvement in overall survival with LMWHs. This apparent benefit then gradually regressed over time toward an absence of the effect of LMWHs on survival (HR: 0.98 [95% confidence interval, 0.93; 1.03]). CONCLUSION: Despite supportive experimental data and early clinical findings, the promising antitumoral effect of LMWHs in patients with cancer gradually vanished over time toward a lack of impact on overall survival. This result suggests 'p-hacking' and selective reporting of the positive results from post hoc subgroup analyses in the early studies.


Assuntos
Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/complicações , Tromboembolia Venosa/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do Tratamento
18.
J Thromb Haemost ; 18(7): 1728-1737, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32299150

RESUMO

BACKGROUND: Detection of severe renal impairment in patients with venous thromboembolism (VTE) is mandatory both for selecting anticoagulant therapy and for evaluating major bleeding risk, increased by severe renal impairment. OBJECTIVES: To determine whether the Cockcroft and Gault (CG) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas identify severe renal impairment in the same VTE patients presenting the same risk of major bleeding. PATIENTS/METHODS: We compared clinical characteristics and outcomes during the first 3 months of anticoagulation between VTE patients in the RIETE registry with severe renal impairment according to the CG and/or CKD-EPI formula (estimated glomerular filtration rate <30 mL/min and <30 mL/min/1.73 m2 , respectively). The primary outcome was major bleeding. RESULTS: Up to October 2017, 41 796 patients were included in RIETE. Among the 4676 patients with severe renal impairment according to at least one of the formulas, this was not confirmed by the other formula in 1904 (40.7%). Major bleeding risk was increased in every patient subgroup with severe renal impairment vs patients without this condition (CG or CKD-EPI < 30: odds ratio [OR] = 2.26, 95% confidence interval [CI 2.01-2.53], only CG < 30: OR = 1.72, 95% CI [1.37-2.13], only CKD-EPI < 30: OR = 2.34, 95% CI [1.77-3.05], CG+CKD-EPI < 30: OR = 2.47, 95% CI [2.16-2.83], all vs CG+CKD-EPI > 30). CONCLUSION: The CG and CKD-EPI formulas identify different subgroups of patients with severe renal impairment, leading to discordant results in 40.7% of these patients. Irrespective of the formula used for their identification, patients with severe renal impairment have a higher risk of major bleeding under anticoagulant therapy.


Assuntos
Insuficiência Renal Crônica , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico
19.
Am J Med ; 133(8): e406-e421, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32333853

RESUMO

BACKGROUND: We aimed to validate the Men Continue and HERDOO2 (HERDOO2), D-dimer, age, sex, hormonal therapy (DASH), and updated Vienna recurrent venous thromboembolism prediction models in a population composed entirely of first unprovoked pulmonary embolism, and to analyze the impact of the addition of the pulmonary vascular obstruction index (PVOI) on score accuracy. METHODS: Analyses were based on the double-blind, randomized PADIS-PE trial, which included 371 unprovoked pulmonary embolism patients initially treated for 6 months, successively randomized to receive an additional 18 months of warfarin or placebo, and subsequently followed-up for 2 years. RESULTS: The HERDOO2, DASH, and updated Vienna scores displayed C-statistics of 0.61 (95% CI 0.54-0.68), 0.60 (95% CI 0.53-0.66), and 0.58 (95% CI 0.51-0.66), respectively. Only the HERDOO2 score identified low recurrence risk patients (<3%/year) after anticoagulation was stopped. When added to either of the prediction models, PVOI measured at pulmonary embolism diagnosis, after 6 months of anticoagulation, or both, improved scores' C-statistics between +0.06 and +0.11 points and consistently led to identifying at least 50% of patients who experienced recurrence but in whom the scores would have indicated against extended anticoagulation. CONCLUSIONS: In patients with a first unprovoked pulmonary embolism, the HERDOO2 score is able to identify patients with a low recurrence risk after treatment discontinuation. Addition of PVOI improves accuracy of all scores. CLINICAL TRIALS REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: NCT00740883.


Assuntos
Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Adulto , Fatores Etários , Idoso , Duração da Terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Embolia Pulmonar/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores Sexuais , Cintilografia de Ventilação/Perfusão , Varfarina/uso terapêutico
20.
N Engl J Med ; 382(20): 1916-1925, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32223113

RESUMO

BACKGROUND: Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients. METHODS: In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding. RESULTS: A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P<0.001 for noninferiority; P = 0.01 for superiority). The incidence of bleeding did not differ significantly between the rivaroxaban group and the enoxaparin group (1.1% and 1.0%, respectively, for major bleeding or nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding). CONCLUSIONS: Rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilization after nonmajor orthopedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.).


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Extremidade Inferior/cirurgia , Procedimentos Ortopédicos , Complicações Pós-Operatórias/prevenção & controle , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Administração Oral , Adulto , Anticoagulantes/efeitos adversos , Método Duplo-Cego , Enoxaparina/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/prevenção & controle , Rivaroxabana/efeitos adversos , Tromboembolia Venosa/mortalidade , Trombose Venosa/prevenção & controle
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