Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.419
Filtrar
1.
Medicine (Baltimore) ; 100(10): e25003, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725878

RESUMO

ABSTRACT: The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events.A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year.Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m2, KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05).Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m2, anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year.


Assuntos
Antitrombinas/administração & dosagem , Doença das Coronárias/cirurgia , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/efeitos adversos , Feminino , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/efeitos adversos , Assistência Perioperatória/efeitos adversos , Assistência Perioperatória/métodos , Hemorragia Pós-Operatória/induzido quimicamente , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Stents , Trombose/etiologia , Trombose/prevenção & controle , Resultado do Tratamento
2.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462055

RESUMO

An early-term infant with uncomplicated perinatal history was found to have a large thrombus in the aortic arch after he failed regular newborn critical congenital heart defect screen. He responded well to bivalirudin thrombolytic and tissue-plasminogen activator (tPA) combination therapy, with a significant resolution of the thrombus. The infant tolerated hospital admission well with no significant complications. He was discharged home on daily aspirin at 2 weeks of life. To our knowledge, the combination therapy approach with bivalirudin and tPA is the first one reported in the literature in the neonatal age group.


Assuntos
Antitrombinas/uso terapêutico , Aorta Torácica , Doenças da Aorta/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Terapia Trombolítica , Trombose/tratamento farmacológico , Fatores Etários , Doenças da Aorta/diagnóstico por imagem , Hirudinas , Humanos , Recém-Nascido , Masculino , Proteínas Recombinantes/uso terapêutico , Trombose/diagnóstico por imagem
4.
Ann Pharmacother ; 55(1): 59-64, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32590908

RESUMO

BACKGROUND: Although heparin has previously been the anticoagulant of choice during mechanical circulatory support (MCS), there is a lack of consistency in dose-response in pediatric patients. Bivalirudin offers more consistent dose-response in adults; however, there are limited data for pediatrics use. OBJECTIVE: The purpose was to characterize the usage, dosage, and safety profile of bivalirudin when used for pediatric MCS in a tertiary care pediatric hospital. METHODS: A retrospective review of pediatric patients receiving bivalirudin for extracorporeal membrane oxygenation/ventricular assist device (ECMO/VAD) anticoagulation was conducted. The primary outcome was the average dose of bivalirudin. Additional outcomes included initial and maximum bivalirudin dose, time to first therapeutic activated partial thromboplastin time (aPTT), time within goal aPTT range, bleeding and clotting complications, and cost. Data were compared between ECMO and VAD patients. RESULTS: Thirty-four patients were included. The median dose of bivalirudin was 0.37 mg/kg/h (interquartile range [IQR] = 0.21-0.56), with a maximum dose of 0.62 mg/kg/h (IQR = 0.33-0.91). VAD patients had a higher median and maximum dose as compared with ECMO patients. Patients achieved their therapeutic goal in a median of 6.1 hours and averaged 61.9% time within therapeutic aPTT. One patient had significant hemorrhage, whereas 3 patients had clotting requiring a circuit change. Bivalirudin acquisition cost was higher than heparin. CONCLUSION AND RELEVANCE: Bivalirudin dosing in ECMO and VAD patients is consistent with dosing seen in previous reports but may be higher in VAD patients. Comparative studies between heparin and bivalirudin are necessary to compare cost-effective outcomes for pediatric patients.


Assuntos
Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Oxigenação por Membrana Extracorpórea , Coração Auxiliar , Fragmentos de Peptídeos/uso terapêutico , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Criança , Pré-Escolar , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Coração Auxiliar/efeitos adversos , Hirudinas/administração & dosagem , Hirudinas/efeitos adversos , Humanos , Masculino , Tempo de Tromboplastina Parcial , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Trombose/etiologia , Trombose/prevenção & controle
5.
J Extra Corpor Technol ; 52(4): 327-331, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33343036

RESUMO

Saddle pulmonary embolism (PE) remains a challenge to diagnose and manage in pediatric patients. Current literature encourages early consideration of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in high-risk PE patients with impending right ventricular failure. We present a 17-year-old patient who was admitted to a pediatric cardiac intensive care unit with saddle PE requiring emergent VA-ECMO support because of cardiovascular collapse. Despite anticoagulation with bivalirudin and receiving systemic thrombolysis with alteplase, the clot burden was persistent with minimal improvement in right ventricular function. We proceeded to catheter thrombolysis while on VA-ECMO. This ultimately led to a successful resolution of the PE and allowed for weaning off VA-ECMO. PE is rare in children compared with adults, and pediatricians may be unaware of therapies becoming increasingly used in adults such as the use of VA-ECMO, with systemic and local thrombolysis. The concurrent use of a direct thrombin inhibitor for ECMO anticoagulation alongside the thrombolysis is a novel combination in this condition and age-group.


Assuntos
Oxigenação por Membrana Extracorpórea , Embolia Pulmonar , Adolescente , Adulto , Criança , Hirudinas , Humanos , Fragmentos de Peptídeos , Embolia Pulmonar/tratamento farmacológico , Proteínas Recombinantes , Ativador de Plasminogênio Tecidual/uso terapêutico
7.
Trials ; 21(1): 769, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895056

RESUMO

OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. TRIAL DESIGN: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. EXCLUSION CRITERIA: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. INTERVENTION AND COMPARATOR: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. BLINDING (MASKING): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). TRIAL STATUS: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antitrombinas/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , /terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hirudinas , Humanos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/sangue , Catar , Proteínas Recombinantes/uso terapêutico
8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 48(8): 648-654, 2020 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-32847320

RESUMO

Objective: To compare the safety and efficacy of bivalirudin versus unfractionated heparin during perioperative period of percutaneous coronary intervention(PCI) in real-world. Methods: A total of 13 097 serial patients who underwent PCI from January 2016 to November 2018 in the Northern Theater Command were enrolled in the present study. Patients were stratified as the bivalirudin group or the heparin group according to antithrombotic therapy during PCI. The primary efficiency endpoint was 30-day net adverse clinical event(NACE), defined as all-cause death, re-infarction, urgent target lesion revascularization (uTLR), stroke or any bleeding. The second efficiency endpoint was 30-day major cardiac and cerebral events (MACCE), defined as all-cause death, re-infarction, uTLR and stroke. Additional end points included the rates of stent thrombosis at 30 days. Propensity scores included clinical and demographic variables, with 1∶2 matching. Compared the incidence of events above between the two groups before and after matching. Results: Among the 13 097 included patients(age was (61±10) years old), 3 421 (26.1%) were female. And 2 734 patients were divided into the bivalirudin group, and 10 363 patients to the heparin group(5 468 after matching). Before propensity score matching, patients in bivalirudin group were older and received higher levels of CRUSADE score than heparin group. These patients were more likely to have hypertension and more with ST-segment elevation acute coronary syndromes(all P<0.05). After propensity score matching, the incidence of 30-day NACE(3.8%(103/2 734) vs.5.0%(271/5 468), P=0.015) and any bleeding (2.0%(54/2 734) vs. 2.8%(151/5 468), P=0.032) in the bivalirudin group were lower than that in the heparin group, but the incidence of MACCE (1.9%(51/2 734) vs. 2.3%(127/5 468), P=0.180) and stent thrombosis (0.1%(2/2 734) vs. 0.1%(3/5 468), P=1.000) were comparable between the two groups. Conclusion: The risk of bleeding and the incidence of NACE are significantly lower for patients using bivalirudin during perioperative period of PCI compared to heparin, without significant differences in ischemic events.


Assuntos
Heparina/uso terapêutico , Intervenção Coronária Percutânea , Idoso , Anticoagulantes/uso terapêutico , Feminino , Hirudinas , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos , Período Perioperatório , Proteínas Recombinantes , Resultado do Tratamento
9.
Am Heart J ; 227: 19-30, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32663660

RESUMO

BACKGROUND: Current guidelines recommend anticoagulation therapy during primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). However, whether anticoagulation should be continued after pPCI has not been well investigated. METHODS/DESIGN: The RIGHT trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in STEMI patients treated with pPCI evaluating the prolongation of anticoagulation after the procedure. Patients are randomized in a 1:1 fashion to receive either prolonged anticoagulant or matching placebo (no anticoagulation) for at least 48 hours after the procedure. When randomized to anticoagulation prolongation, the patient is assigned to intravenous unfractionated heparin (UFH) or subcutaneous enoxaparin or intravenous bivalirudin (same drug and same regimen at each center). The primary efficacy endpoint is the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, stent thrombosis (definite) or urgent revascularization (any vessel) at 30 days. The primary safety endpoint is major bleeding (BARC 3-5) at 30 days. Based on a superiority design and assuming a 35% relative risk reduction (from 7% to 4.5%), 2856 patients will be enrolled, accounting for a 5% drop-out rate (α = 0.05 and power = 80%). CONCLUSION: The RIGHT trial tests the hypothesis that post-procedural anticoagulation is superior to no anticoagulation in reducing ischemic events in STEMI patients undergoing pPCI.


Assuntos
Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Heparina/administração & dosagem , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto/métodos , Período Pós-Operatório , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Fatores de Tempo
10.
Circ Cardiovasc Interv ; 13(6): e008702, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32527190

RESUMO

BACKGROUND: Procedural anticoagulation with bivalirudin (BIV), trans-radial intervention (TRI), and use of a vascular closure device (VCD) are thought to mitigate percutaneous coronary intervention (PCI)-related bleeding. We compared the impact of these bleeding avoidance strategies (BAS) for PCIs stratified by bleeding risk. METHODS: We performed a retrospective cohort analysis of PCIs from 18 facilities within one health care system from 2009Q3 to 2017Q4. Bleeding risk was assessed per the National Cardiovascular Data Registry CathPCI bleeding model, with procedures stratified into 6 categories (first, second, third quartiles, 75th-90th, 90th-97.5th, and top 2.5th percentiles). Regression models were used to assess the impact of BAS on bleeding outcome. RESULTS: Of 74 953 PCIs, 9.4% used no BAS, 12.0% used BIV alone, 20.8% used TRI alone, 26.8% used VCD alone, 5.4% used TRI+BIV, and 25.6% used VCD+BIV. The crude bleeding rate was 4.4% overall. Only 2 comparisons showed significant trends across all risk strata: VCD+BIV versus no BAS, odds ratio (95% CI) range: first quartile, 0.36 (0.18-0.72) to top 2.5th percentile, 0.50 (0.32-0.78); TRI versus no BAS, odds ratio (95% CI) range: first quartile, 0.15 (0.06-0.38) to top 2.5th percentile, 0.49 (0.28-0.86). TRI had lower odds of bleeding compared with BIV for all risk strata except the top 2.5th percentile. Addition of BIV to TRI did not change the odds of bleeding for any risk strata. Factors potentially limiting use of TRI (renal failure, shock, cardiac arrest, and mechanical circulatory support) were present in ≤10% of procedures below the 90th percentile. CONCLUSIONS: Among individual BAS, only TRI had consistently lower odds of bleeding across all risk strata. Factors potentially limiting TRI were found infrequently in procedures below the 90th percentile of bleeding risk. For transfemoral PCI, VCD+BIV had lower odds of bleeding compared with no BAS across all risk strata.


Assuntos
Antitrombinas/administração & dosagem , Cateterismo Periférico , Hemorragia/prevenção & controle , Técnicas Hemostáticas , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Artéria Radial , Idoso , Antitrombinas/efeitos adversos , Cateterismo Periférico/efeitos adversos , Feminino , Técnicas Hemostáticas/efeitos adversos , Técnicas Hemostáticas/instrumentação , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Punções , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Estados Unidos , Dispositivos de Oclusão Vascular
11.
Life Sci ; 255: 117779, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32417374

RESUMO

OBJECTIVE: Kidney is the most common location of microangiopathy in diabetic patients, and we designed this study to investigate the effects of hirudin on renal microangiopathy in STZ-induced diabetes rats and in vitro. METHODS: We established a diabetes model by intraperitoneal injection of STZ and administered hirudin daily by subcutaneous injection. HE staining was used to assess kidney pathological changes. Western blot and immunochemistry was used to detect the protein expression. Glomerular endothelial cells (GEC) in normal rats were assessed by cell scratch test for migration ability and tubule formation experiment for angiogenesis ability. RESULTS: Compared with DN rats without any treatment, the serum creatinine, serum Cys C, 24-hour urine protein of DN rats with hirudin treatment were significantly decrease, the kidney/body weight and glomerular area of DN rats with hirudin treatment were all significantly decrease, and also significant improvement in renal pathology revealed by HE staining in DN rats after treating with hirudin. Moreover, we also found that hirudin coun not only significantly increase the prothrombin time and aivated partial thromboplastin time in DN rats, but also significantly decrease the expression of VEGF and TM-1 protein in kidney tissues of DN rats. In vitro, we found that high glucose could promote the migration and angiogensis of GEC, and significantly increased the expression of VEGF and Ang protein, but significantly decreased the expression of THBS1 and Arg1 protein. More importantly was that hirudin could inhibit the migration and angiogensis of GEC, and reversed HG-induced the expression of VEGF, Ang, THBS1 and Arg1 protein in GEC. In addition, we also found that hirudin could not only decrease HG-enhanced the activity of RhoA in GEC, but also decrease HG-enhanced the expression of p-MYPT1/MYPT1, p-p38/p38 protein in GEC. CONCLUSION: Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes, and might be related to hirudin inhibiting glomerular endothelial cell migration and angiogenesis through Rho-kinase and subsequent p38MAPK/NF-kB signaling pathway.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/prevenção & controle , Hirudinas/farmacologia , Neovascularização Patológica/prevenção & controle , Animais , Movimento Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Glucose/metabolismo , Glomérulos Renais/metabolismo , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Quinases Associadas a rho/metabolismo
12.
Parasitol Res ; 119(6): 1767-1775, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363441

RESUMO

The hirudin-like factors 3 (HLF3) and 4 (HLF4) belong to a new class of leech-derived factors and are present in specimens of the three European medicinal leeches, Hirudo medicinalis, Hirudo verbana, and Hirudo orientalis, respectively. Here we describe the functional analysis of natural and synthetic variants of HLF3 and HLF4. Whereas the natural variants display only very low or no detectable anti-coagulatory activities, modifications within the N-termini in combination with an exchange of the central globular domain have the potency to greatly enhance the inhibitory effects of respective HLF3 and HLF4 variants on blood coagulation. Our results support previous observations on the crucial importance of all parts (both the N- and C-termini as well as the central globular domains) of hirudin and HLF molecules for thrombin inhibition.


Assuntos
Hirudinas/metabolismo , Sanguessugas/química , Sequência de Aminoácidos , Animais , Coagulação Sanguínea , Hirudinas/química , Hirudinas/genética , Hirudo medicinalis/química , Hirudo medicinalis/genética , Sanguessugas/classificação , Sanguessugas/genética , Domínios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , Trombina/antagonistas & inibidores
13.
Adv Gerontol ; 33(1): 87-91, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32362089

RESUMO

A study is presented on the effectiveness and safety of various anticoagulants used in patients of an older age group with acute coronary syndrome during percutaneous coronary interventions. Bivalirudin was shown to be highly effective in comparison with unfractionated heparin and monafram in relation to the amount of bleeding that occurs in the postoperative period and adverse cardiovascular complications.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anticoagulantes/uso terapêutico , Intervenção Coronária Percutânea , Idoso , Anticorpos Monoclonais/uso terapêutico , Hemorragia , Heparina/uso terapêutico , Hirudinas , Humanos , Fragmentos de Peptídeos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
14.
Chin J Integr Med ; 26(3): 197-204, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32180149

RESUMO

OBJECTIVE: To investigate protective effects of hirudin on oxidative stress and apoptosis of spinal dorsal root ganglion cells in high-glucose rats at the cellular and molecular level. METHODS: Dorsal root ganglion neurons (DRGn) were harvested from embryonic day in 15 SD rats, purified and identificated after primary culture. They were divided into the normal control group, high-glucose (HG) group, positive control (alpha-lipoic acid, ALA) group, low-dose hirudin group (H1), medium-dose hirudin group (H2) and high-dose hirudin group (H3). The control group was cultured by neuron specific culture medium, while the HG group was cultured by neuron specific culture medium and 20 mmol/L glucose (HG medium). The hirudin groups were cultured by HG medium+0.25 IU/mL hirudin (H1), HG medium+0.5 IU/mL hirudin (H2) and HG medium+1 IU/mL hirudin (H3). The ALA group was cultured by HG medium+100 µ mol/L ALA. 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenylt etrazolium bromide (MTT) assay was used to explore the optimum concentration and intervention time. Flow cytometry assay was used to detect the level of reactive oxygen series (ROS). Western blot and quantificational realtime polymerase chain reaction (qRT-PCR) were used to detect the expression of protein and mRNA of nuclear factor erythroid 2-related factor 2 (Nrf-2), hemeoxygence-1 (HO-1), nuclear factor-κ B (NF-κ B) and Caspase-3. TUNEL assay was used to test the apoptosis rate of different groups. RESULTS: After 24 h of culture, the cell activity of hirudin and ALA groups were higher than that of HG group, and there was a statistical difference between the H1 group and HG group (P<0.05). In hirudin groups, the apoptosis rate of cells, the expression of activated Caspase-3 protein and Caspase-3 mRNA were lower than those of HG group (P<0.01), higher than those of ALA group (P<0.01 or P<0.05). The ROS level of hirudin groups was higher than that of ALA group (P<0.01), lower than that of HG group (P<0.01 or P<0.05). The expression of NF-κ B (P65) protein in H3 group were lower than those of HG group (P<0.05). The expression of Nrf-2 protein in hirudin groups was higher than that of HG group (P<0.01), lower than that of ALA group (P<0.01 or P<0.05). The expression of HO-1 protein in hirudin groups was lower than that of ALA group (P<0.01 or P<0.05), higher than that of HG group (P<0.01 or P<0.05). CONCLUSIONS: The activity of DRGn cells can be promoted by hirudin under HG conditions. The effects of hirudin on the inhibition of HG on DRGn cells damage mainly include scavenging ROS, up-regulating Nrf-2/HO-1 pathway, inhibiting activation of NF-κ B pathway, down-regulating the expression of and Caspase-3 and reducing DRGn cell apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Gânglios Espinais/efeitos dos fármacos , Hirudinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Caspase 3/metabolismo , China , Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismo
15.
Circ Cardiovasc Interv ; 13(4): e008671, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32216471

RESUMO

BACKGROUND: Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients. METHODS: A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days. RESULTS: The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke. CONCLUSIONS: In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.


Assuntos
Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Fragmentos de Peptídeos/uso terapêutico , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Trombose Coronária/mortalidade , Trombose Coronária/prevenção & controle , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Masculino , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Recidiva , Sistema de Registros , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Suécia , Fatores de Tempo , Resultado do Tratamento
16.
Cardiovasc Drugs Ther ; 34(1): 101-111, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32100149

RESUMO

PURPOSE: The aim of this study was to explore the safety and efficacy of bivalirudin in elderly patients undergoing percutaneous coronary intervention (PCI). METHODS: An electronic search was conducted for randomized controlled trials with outcomes of interest in the elderly (≥ 65 years of age). Pooled risk ratios (RR) and 95% confidence interval (CI) using random effects Der Simonian-Laird models were calculated. Primary outcomes were net adverse clinical events (NACE) and major bleeding events at 30 days. Secondary outcomes were major adverse cardiac events (MACE) at 30 days. MACE, all-cause mortality, and NACE at 6-12 months were also examined. RESULTS: Eleven trials that randomized a total of 15,895 elderly patients undergoing PCI to bivalirudin versus heparin were included. At 30 days, bivalirudin was associated with a reduced risk of NACE (0.86 [0.75-0.99], p = 0.04), mainly driven by reduction in major bleeding events (0.66 [0.54-0.80], p < 0.0001), as compared with heparin. On subgroup analyses based on the use of GPI in the heparin arm, benefit of major bleeding associated with bivalirudin appeared to be equally evident when GPI was used as a bailout (0.66 [0.46-0.94], p = 0.02) versus routine (0.67 [0.51-0.88], p = 0.004) adjunctive therapy with heparin. Subgroup analyses stratified by clinical presentation showed that benefit of bivalirudin in reducing NACE was even more obvious in the elderly group presenting with ST segment elevation myocardial infarction (STEMI) (0.76 [0.65-0.89], p = 0.0007), as compared with the overall (acute coronary syndrome or stable ischemic heart disease) group. No difference in MACE (0.94 [0.82-1.09], p = 0.42) was demonstrated between the two groups. Bivalirudin was associated with a similar risk of NACE (0.74 [0.39-1.42], p = 0.36) at 6 months and MACE (0.90 [0.68-1.19], p = 0.45) at 6-12 months, while a non-statistically significant trend toward lower all-cause mortality (0.70 [0.47-1.06], p = 0.09) at 1 year. CONCLUSION: In elderly patients undergoing PCI, bivalirudin was associated with a lower risk of major bleeding events and the magnitude of benefit was not related to the use of GPI and irrespective of clinical presentation. Bivalirudin may reduce the NACE, particularly in elderly patients presenting with STEMI or in the setting of routine GPI use in the heparin arm, while no difference in MACE was demonstrated between the two groups.


Assuntos
Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Doença da Artéria Coronariana/terapia , Heparina/administração & dosagem , Fragmentos de Peptídeos/uso terapêutico , Intervenção Coronária Percutânea , Fatores Etários , Idoso , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Masculino , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
Am J Cardiol ; 125(8): 1142-1147, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32087994

RESUMO

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Anemia/epidemiologia , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Hemorragia Pós-Operatória/epidemiologia , Síndrome Coronariana Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angina Instável/epidemiologia , Angina Instável/cirurgia , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Aspirina/uso terapêutico , Causas de Morte , Clopidogrel/uso terapêutico , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Stents Farmacológicos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/mortalidade , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/mortalidade , Heparina/uso terapêutico , Hirudinas , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/mortalidade , Estimativa de Kaplan-Meier , Masculino , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/cirurgia , Fragmentos de Peptídeos/uso terapêutico , Cuidados Pós-Operatórios , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/mortalidade , Cloridrato de Prasugrel/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Medição de Risco , Stents , Ticagrelor/uso terapêutico , Doenças Urológicas/induzido quimicamente , Doenças Urológicas/epidemiologia , Doenças Urológicas/mortalidade
18.
J Card Surg ; 35(4): 779-786, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32048330

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) induces hemostatic alterations that may contribute to hematological complications. Unfractionated heparin (UFH) is the mainstay antithrombotic in ECMO and depends on antithrombin III (AT III) to exhibit its actions. However, it bears the risk for heparin-induced thrombocytopenia. Bivalirudin is a direct thrombin inhibitor and is inherently not dependent on AT III. AIM OF THE STUDY: To assess the efficacy and safety profiles of UFH compared with bivalirudin during ECMO support. METHODS: We retrospectively reviewed 52 adult patients who were supported by ECMO from 1 January 2013 to 1 September 2018. Among them, 33 received UFH and 19 received bivalirudin. We analyzed their 7-day rate of composite thrombotic, bleeding, and mortality episodes while on anticoagulation. RESULTS: There were no statistical differences in the 7-day rate of composite thrombosis (33.3% vs 26.3%; P = 0.60), major bleeding (18.2% vs 5.3%; P = .24), 30-day mortality, (42.4% vs 26.3%; P = .37), or in-hospital mortality (45.5% vs 36.8%; P = .58). The percentage of time activated partial thromboplastin time (aPTT) was within the therapeutic range was higher with bivalirudin (50% vs 85.7%; P = .007). CONCLUSIONS: This study suggests that UFH and bivalirudin are associated with similar rates of thrombosis, major bleeding, and mortality events in patients supported by ECMO. However, it was observed that bivalirudin consistently maintained aPTT within the therapeutic range in comparison to UFH.


Assuntos
Anticoagulantes/administração & dosagem , Oxigenação por Membrana Extracorpórea/efeitos adversos , Heparina/administração & dosagem , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Trombose/etiologia , Trombose/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Adulto Jovem
19.
Medicine (Baltimore) ; 99(6): e19064, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028428

RESUMO

BACKGROUND: This meta-analysis is to evaluate the efficacy and safety of bivalirudin in patients with ST-elevation myocardial infarction (STEMI). METHODS: PubMed, Cochrane Library, Embase, CNKI, CBMdisc, and VIP database were searched. Randomized controlled trial (RCT) was selected and the meta-analysis was conducted by RevMan 5.1. The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE) and the primary safety endpoint was the incidence of major bleeding. Secondary efficacy endpoints were myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST), stock, mortality, and thrombocytopenia. The pooled risk ratios (RRs) with the corresponding 95% confidence intervals (CI) were used to assess the efficacy and safety of bivalirudin vs heparin. RESULTS: Seven RCTs met the inclusion criteria, and 16,640 patients were included. We found that bivalirudin associated with lower risk of mortality (RR = 1.05; 95% CI = 0.74-1.49; P = .03; I = 2%), major bleeding (RR = 0.64; 95% CI = 0.54-0.75; P < .00001; I = 70%) and thrombocytopenia (RR = 0.39; 95% CI = 0.25-0.61; P < .0001; I = 0) compared with heparin. However, the use of bivalirudin increase the risk of MI(RR = 1.37; 95% CI = 1.10-1.71; P = .004; I = 25%) and ST(RR = 1.61; 95% CI = 1.05-2.47; P = .03; I = 70%) and has similar risk of MACE (RR = 1.00; 95% CI = 0.90-1.11; P = .97; I = 16%), TVR (RR = 1.43; 95% CI = 0.92-2.22; P = .11; I = 46%) and stock (RR = 1.43; 95% CI = 0.92-2.22; P = .11; I = 46%) compared with heparin used in STEMI patients. CONCLUSION: Bivalirudin associated with lower risk of mortality, major bleeding and thrombocytopenia compared with heparin. However, the use of bivalirudin increase the risk of MI and ST and has similar risk of MACE, TVR and stock compared with heparin used in STEMI patients.


Assuntos
Antitrombinas/uso terapêutico , Doença das Coronárias/cirurgia , Heparina/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Intervenção Coronária Percutânea , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Trombose/etiologia , Trombose/prevenção & controle , Resultado do Tratamento
20.
BMJ Case Rep ; 13(1)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31915185

RESUMO

A 48-year-old male patient requiring extracorporeal membrane oxygenation (ECMO) support for hypoxaemic respiratory failure failed to achieve therapeutic anticoagulation with bivalirudin after continuous dose escalations, and continued to have recurrent fibrin stranding in the circuit over a 6-day course of treatment. Suspecting bivalirudin resistance, the patient was transitioned to argatroban and achieved a therapeutic response in less than 24 hours. The case describes the challenges of anticoagulation in ECMO supported patients. The interplay between bivalirudin metabolism, renal replacement therapy, and immunological effects leading to a heparin-like-effect, inflammatory mediators, and thrombotic burdens may all impact the clinical effect during bivalirudin therapy. The structural biochemistry of thrombin and bivalirudin likely plays a role in the presented patient's successful response to argatroban. Bivalirudin may fail at achieving therapeutic anticoagulation in patients with genetic thrombin mutations or structural defects that alter the binding pockets at the thrombin exosites.


Assuntos
Anticoagulantes/uso terapêutico , Resistência a Medicamentos , Oxigenação por Membrana Extracorpórea , Fragmentos de Peptídeos/uso terapêutico , Ácidos Pipecólicos/uso terapêutico , Insuficiência Respiratória/terapia , Arginina/análogos & derivados , Terapia Combinada , Hirudinas , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Sulfonamidas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...