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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.
Medicine (Baltimore) ; 100(12): e24522, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761634

RESUMO

BACKGROUND: The intracranial hemorrhage (ICH) risk of oral anticoagulants/non-vitamin K antagonist oral anticoagulants (NOACs) remains largely unknown. Patients who need oral anticoagulants such as aspirin or warfarin often suffer from obvious complications. METHODS: This network meta-analysis intended to assess the ICH risk in patients taking NOACs. The data from PubMed, the Cochrane database, and Embase were reviewed. All phase III randomized controlled trials of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), aspirin and warfarin were reviewed. RESULTS: Twenty-three trials involving 137,713 participants were included, involving 6 regimens. Warfarin had the first risk of ICH (surface under the cumulative ranking area: 0.82), followed by dabigatran, edoxaban, aspirin, apixaban, rivaroxaban, and placebo. Dabigatran had the lowest risk of all-cause mortality (surface under the cumulative ranking area: 0.63), followed by apixaban, edoxaban, warfarin, rivaroxaban, aspirin, and placebo. CONCLUSION: Warfarin significantly increased the risk of ICH in patients taking oral anticoagulants compared with 4 NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) and aspirin. Apixaban is least likely to induce all-cause mortality.


Assuntos
Antitrombinas/efeitos adversos , Aspirina/efeitos adversos , Hemorragias Intracranianas/epidemiologia , Varfarina/efeitos adversos , Administração Oral , Antitrombinas/administração & dosagem , Aspirina/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Humanos , Hemorragias Intracranianas/induzido quimicamente , Mortalidade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco/estatística & dados numéricos , Varfarina/administração & dosagem
4.
Clin Appl Thromb Hemost ; 26: 1076029620954913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33030036

RESUMO

INTRODUCTION: Sulodexide represents a mixture of fast-moving heparin (FMH) and dermatan sulfate (DS) and has been used for the management of venous diseases such as DVT and related disorders. The purpose of this study is to compare sulodexide and its components with unfractionated heparin (UFH) to determine its suitability for the indications in which UFH is used. MATERIALS AND METHOD: Active pharmaceutical ingredients (API) versions of sulodexide, FMH and DS were obtained from Alfasigma. API versions of UFH were obtained from Medefil Inc. Normal human citrated plasma was obtained from blood bank of the Loyola University Medical Center. Each of the individual agents were supplemented in plasma at a graded concentration of 0.0-10 µg/mL. Clotting assays (PiCT, aPTT, PT and TT), anti-Xa and anti-IIa and thrombin generation studies were carried out. Results were compiled as mean ± SD of 3 individual determination. RESULT: In the clot based (PiCT, aPTT and TT), anti-Xa and IIa assays, both the UFH and FMH produced stronger activities in these assays followed by sulodexide. DS did not show any anticoagulant activity. In the thrombin generation assay, FMH and UFH produced comparable inhibition of thrombin generation as measured by various parameters. Sulodexide was slightly weaker in this assay, whereas DS produced relatively weaker effects. CONCLUSION: In comparison to sulodexide, both UFH and FMH exhibit comparable anticoagulant activity despite differences in their molecular weight. These results suggest that sulodexide can be developed as a parenteral anticoagulant for indications in which UFH is used.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Glicosaminoglicanos/farmacologia , Trombina/farmacologia , Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Antitrombinas/farmacologia , Glicosaminoglicanos/administração & dosagem , Heparina/administração & dosagem , Heparina/farmacologia , Humanos , Itália , Sensibilidade e Especificidade , Trombina/administração & dosagem
5.
Int Heart J ; 61(5): 905-912, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921660

RESUMO

There is little data on management and outcomes of atrial fibrillation (AF) patients on direct oral anticoagulants (DOAC) undergoing general surgery.We retrospectively assessed 98 surgeries in 85 nonvalvular AF patients aged 73 ± 8 (59 men) receiving DOACs. Cardiac, emergency, and minimally invasive surgeries were excluded.The CHA2DS2-VASc score ranged from 0 to 8. The DOACs being given were: dabigatran, 16; rivaroxaban, 25; apixaban, 28; and edoxaban, 16. While the DOACs were not suspended in 11 cases, they were interrupted for a median of 2.0 days before surgery and restarted at a median of 3.0 days after surgery. There were 9 complications (9.2%), 3 instances of thromboembolism and 6 bleeding. Thromboembolism occurred at a mean of 3.0 postoperative days, all of which occurred before resumption of DOACs, while bleeding events occurred at a mean of 4.0 postoperative days. Two of the 3 patients with thromboembolism went into cardiopulmonary arrest during the event, but were resuscitated. There were significantly more patients with congestive heart failure or combined antiplatelets in the patients with complications. The complication group had a significantly higher HAS-BLED score and lower preoperative hemoglobin level. There were no significant differences in the management of DOAC interruption between those with complications and without.The perioperative complication rate in nonvalvular AF patients undergoing elective surgery treating with DOACs was 9.2%. Patients with congestive heart failure, receiving combined therapy with antiplatelets, a higher HAS-BLED score, or lower preoperative hemoglobin level were at higher risk. Further studies evaluating the ideal perioperative DOAC protocol are warranted.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Doenças das Artérias Carótidas/epidemiologia , Infarto Cerebral/epidemiologia , Inibidores do Fator Xa/administração & dosagem , Infarto do Miocárdio/epidemiologia , Assistência Perioperatória/métodos , Hemorragia Pós-Operatória/epidemiologia , Tromboembolia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Fibrilação Atrial/complicações , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Dabigatrana/administração & dosagem , Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Eletivos , Embolia/epidemiologia , Endoscopia , Feminino , Humanos , Masculino , Procedimentos Ortopédicos , Complicações Pós-Operatórias/epidemiologia , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Piridonas/administração & dosagem , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Tiazóis/administração & dosagem , Tromboembolia/etiologia , Procedimentos Cirúrgicos Urológicos , Procedimentos Cirúrgicos Vasculares
6.
Medicine (Baltimore) ; 99(36): e22084, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899083

RESUMO

RATIONALE: Dabigatran is a direct thrombin inhibitor that is widely used to prevent the formation of thrombus formation. Amiodarone can increase the plasma concentration of dabigatran. CES1 (carboxylesterase 1) and ABCB1 (ATP-binding cassette subfamily B member 1) genetic polymorphisms associate with the pharmacokinetics of dabigatran. PATIENT CONCERNS: A 62-year-old woman was admitted to the hospital due to chest tightness, fatigue, and discomfort despite long-term anticoagulation with dabigatran 110 mg twice daily for 6 months, with concomitant use of amiodarone. DIAGNOSES: Left atrial appendage thrombus formation with a history of atrial fibrillation. INTERVENTIONS: The clinician changed dabigatran to warfarin. To explore the causes of insufficient anticoagulation using dabigatran in this patient, we examined the ABCB1 and CES1 genes. Results showed that she carried ABCB1 variant alleles with 3 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs1045642, rs2032582) and CES1 variant alleles with 2 heterozygote SNPs (rs2244613, rs4580160). OUTCOMES: The left atrial appendage thrombus disappeared. LESSONS: Multiple mutations in the ABCB1 and CES1 genes may influence the pharmacokinetics of dabigatran and could have contributed to the thrombus formation in the left atrial appendage.


Assuntos
Apêndice Atrial/patologia , Fibrilação Atrial/complicações , Hidrolases de Éster Carboxílico/genética , Trombose/etiologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Antitrombinas/administração & dosagem , Antitrombinas/farmacocinética , Apêndice Atrial/diagnóstico por imagem , Dabigatrana/administração & dosagem , Dabigatrana/farmacocinética , Feminino , Humanos , Pessoa de Meia-Idade , Trombose/prevenção & controle
8.
Arch Cardiovasc Dis ; 113(10): 642-651, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32712202

RESUMO

Major thromboembolic complications in patients with atrial fibrillation, secondary to thromboembolism from the left atrium or the left atrial appendage, are a major concern because of their burden of disabling stroke and mortality. To date, non-vitamin K antagonist oral anticoagulants (NOACs) are considered the first-line strategy in most patients with atrial fibrillation receiving chronic anticoagulation, as they have major advantages compared with vitamin K antagonists, including minimization of intracranial bleeding risk. Although several studies and post-hoc analyses have provided initial data on the use of NOACs in patients with documented atrial and/or left atrial appendage thrombosis, the benefit of NOACs in these patients has not been fully elucidated. In this review, we reappraise current evidence supporting the use of NOACs in patients with established atrial and/or left atrial appendage thrombosis, discussing potential mechanisms favouring the use of a NOAC-based strategy in this special setting.


Assuntos
Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Trombose/tratamento farmacológico , Administração Oral , Antitrombinas/efeitos adversos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Medicina Baseada em Evidências , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Tromboembolia/epidemiologia , Tromboembolia/fisiopatologia , Trombose/epidemiologia , Trombose/fisiopatologia , Resultado do Tratamento
9.
PLoS One ; 15(7): e0235511, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645042

RESUMO

BACKGROUND: There is recent new evidence regarding the combined use of direct oral antiocoagulants and antiplatelet agents in patients with Atrial Fibrillation undergoing PCI. PURPOSE: To compare the efficacy of dual antithrombotic treatment (DAT) including a direct oral anticoagulant (DOAC) and an antiplatelet agent versus triple antithrombotic treatment (TAT) with a vitamin K antagonist (VKA). DATA SOURCES: PubMed, SCOPUS and Google Scholar from through 09/09/2019; references of eligible studies; relevant scientific sessions abstracts and cardiology websites. STUDY SELECTION: Randomized controlled trials that compared DAT including a DOAC with TAT including a VKA and that reported at least the rates of stroke, Stent thrombosis and bleeding. DATA EXTRACTION: Two investigators independently extracted study data and assessed study quality. DATA SYNTHESIS: Four randomized trials that compared DAT including a DOAC with TAT including a VKA were available. Among these, one trial included two independent treatment arms with different DOAC dose, both compared against TAT. For this reason, the two arms were treated independently, resulting in 5 randomized comparisons available for meta-analysis, with a total of 8654 patients involved. The primary safety endpoint was significantly lower in the DAT arm (14.4%) compared to the TAT arm (23%) (RD = -0.08; p<0.001). In addition, we found no significant difference in the incidence of stroke between the treatment arms (p = 0.23). Similarly, no significant difference in the incidence of Stent Thrombosis between the treatment arms (p = 0.08). LIMITATIONS: All trials included were open-label, even though data were blindly analyzed. Qualifying criteria are heterogeneous. CONCLUSIONS: Compared TAT including a VKA, a therapeutic DAT regimen including a DOAC was associated with a significant reduction of the primary safety endpoint in AF patients undergoing PCI with stent implantation for an ACS or chronic coronary syndrome, while no significant difference was found in the rate of ischemic adverse events, including stroke, acute myocardial infarction or stent thrombosis.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Antitrombinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Síndrome Coronariana Aguda/cirurgia , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Fibrilação Atrial/cirurgia , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos , Inibidores da Agregação de Plaquetas/administração & dosagem
10.
J Stroke Cerebrovasc Dis ; 29(8): 104924, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689602

RESUMO

Dabigatran is an orally active direct thrombin inhibitor, initially approved by FDA for the prophylaxis of stroke and systemic embolism in the setting of non-valvular atrial fibrillation (NVAF). Major bleeding is its most common adverse event which is of great concern. However, other types of adverse events such as esophagitis, esophageal ulcer, exanthem and pustular eruptions were reported increasingly in recent years. We present a case of immune hemolytic anemia (IHA) due to dabigatran use in a 72-year-old male with NVAF. This new and rare reported type of adverse event associated with dabigatran suggests that dabigatran may be a new cause of drug-induced immune hemolytic anemia (DIIHI).


Assuntos
Anemia Hemolítica Autoimune/induzido quimicamente , Antitrombinas/efeitos adversos , Dabigatrana/efeitos adversos , Idoso , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/imunologia , Antitrombinas/administração & dosagem , Doença Crônica , Dabigatrana/administração & dosagem , Progressão da Doença , Substituição de Medicamentos , Glucocorticoides/administração & dosagem , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Resultado do Tratamento , Varfarina/administração & dosagem
11.
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
12.
Cardiovasc Drugs Ther ; 34(4): 555-568, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32350792

RESUMO

Ischaemic stroke and systemic embolism are the major potentially preventable complications of atrial fibrillation (AF) leading to severe morbidity and mortality. Anticoagulation using vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOACs) is mandatory for stroke prevention in AF. Following approval of the four NOACs dabigatran, rivaroxaban, apixaban, and edoxaban, the use of VKA is declining steadily. Increasing age with thresholds of 65 and 75 years is a strong risk factor when determining annual stroke risk in AF patients. Current recommendations such as the "2016 Guidelines for the management of atrial fibrillation" of the European Society of Cardiology and the "2019 AHA/ACC/HRS Focused Update" by the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society strengthen the importance of anticoagulation and detection of bleeding risks, of which older age is an important one. While patients aged ≥ 75 years are usually underrepresented in randomised clinical trials, they represent almost 40% of the trial populations in the large NOAC approval studies. Therefore, a sufficient amount of data is available to assess the efficacy and safety for this patient cohort in that specific indication. In this article, the evidence for stroke prevention in AF using either VKA or NOACs is summarised with a special focus on efficacy compared to bleeding risk in patients aged ≥ 75 years. Specifically, we used a model of increased weighing of intracranial bleeding to illustrate the potential benefit of NOACs over VKA in the elderly population. In brief, there are at least two tested strategies with apixaban and edoxaban which even confer an additional clinical net benefit compared with VKA. Furthermore, elderly subgroups of trials for combined antithrombotic treatment following percutaneous coronary interventions in anticoagulated patients are analysed.


Assuntos
Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Dabigatrana/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Piridonas/administração & dosagem , Fatores de Risco , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Tiazóis/administração & dosagem , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem
13.
Ulus Travma Acil Cerrahi Derg ; 26(3): 343-350, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32436968

RESUMO

BACKGROUND: Management of the skin degloving injuries is still a problematic issue, and the avulsed part of the skin may become necrotic. We hypothesized that the anticoagulant pharmacological agents, fondaparinux and dabigatran may be beneficial in the treatment of degloving injuries by enhancing the viability of the reattached flap. METHODS: Twenty four Wistar rats were divided into three groups as follows: control group (Group 1), fondaparinux group (Group 2) and dabigatran group (Group 3). A model of a degloving injury on the tail of rats was developed in all groups. After 15 minutes, the avulsed flaps were sutured back. Group 1 received 1ml/day saline intraperitoneally for 10 days. Group 2 received 0.3 ml/kg/day fondaparinux intraperitoneally for 10 days. Group 3 received 30 mg/kg/day dabigatran orally for 10 days. At the end of the treatments, gross morphological and histopathological tail tissue survivals were evaluated. RESULTS: Histopathological examination of the fondaparinux and dabigatran groups revealed that the tail skin was mostly viable with mild inflammation. The mean necrotic length in tails and severity of inflammation was significantly higher in the control group compared to the fondaparinux and dabigatran groups (p<0.05). No statistically significant differences were noted between the fondaparinux and dabigatran groups in histopathologic evaluations. There was no significant difference in necrosis lengths and the other histopathological parameters between dabigatran and fondaparinux groups. CONCLUSION: Dabigatran and fondaparinux improved tissue survival in skin degloving injuries concerning gross morphological and histopathological findings. However, the findings of this study should be supported and improved by new experimental and especially clinical studies.


Assuntos
Antitrombinas , Dabigatrana , Desenluvamentos Cutâneos , Fondaparinux , Animais , Antitrombinas/administração & dosagem , Antitrombinas/uso terapêutico , Dabigatrana/administração & dosagem , Dabigatrana/uso terapêutico , Desenluvamentos Cutâneos/tratamento farmacológico , Desenluvamentos Cutâneos/patologia , Fondaparinux/administração & dosagem , Fondaparinux/uso terapêutico , Masculino , Ratos , Ratos Wistar , Cauda/lesões
16.
Open Heart ; 7(1): e001232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341789

RESUMO

Objective: To assess the safety (ie, risk of bleeding) and effectiveness (ie, risk of stroke/systemic embolism (SE)) separately for four non-vitamin K oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) versus warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF), including those at high risk of bleeding and treated with reduced doses of NOACs. Methods: We conducted a retrospective analysis of electronic health records and claims data from 372 acute care hospitals in Japan for patients with NVAF newly initiated on NOACs or warfarin. Baseline characteristics were balanced using inverse probability of treatment weighting with stabilised weights (s-IPTW). Bleeding risk and stroke/SE risk were expressed as HRs with 95% CIs. Two sensitivity analyses were conducted. Results: A total of 73 989 patients were eligible for analysis. Notably, 52.8%-81.9% of patients received reduced doses of NOACs. After applying s-IPTW, patient characteristics were well balanced across warfarin/NOAC cohorts. The mean within-cohort age, CHADS2 score and CHA2DS2-VASc score were 76 years, 2.2-2.3 and 3.8, respectively. In all age categories, the majority of the HRs for major bleeding, any bleeding and stroke/SE were equal to or below 1 for all NOACs versus warfarin. Apixaban was the only NOAC associated with a significantly lower risk of any bleeding. There was a trend towards increased risk reduction with NOACs versus warfarin in patients with body weight ≥60 kg. In patients with renal disease, the HRs for apixaban versus warfarin were below 1 for major bleeding, any bleeding and stroke/SE, with statistical significance observed for the risk reduction in stroke/SE versus warfarin. In the sensitivity analysis, there were no large differences in HRs between the two observational periods. Conclusions: In patients with NVAF primarily treated with reduced-dose NOACs, the risks of stroke/SE and major bleeding were significantly lower with NOACs versus warfarin.


Assuntos
Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Demandas Administrativas em Assistência à Saúde , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Dabigatrana/administração & dosagem , Registros Eletrônicos de Saúde , Feminino , Hemorragia/induzido quimicamente , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Piridonas/administração & dosagem , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Tiazóis/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos
17.
Life Sci ; 252: 117665, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32305521

RESUMO

AIMS: Thrombin formation is increased in patients with acute cerebral ischemic stroke, and augments coagulation and inflammation in the brain. Administration of antithrombin (AT) was previously reported to be protective against renal and myocardial ischemic injury. Thus, we hypothesized that treatment with AT would be neuroprotective against cerebral ischemic injury. This study evaluated the effects of AT treatment on ischemic inflammation and brain damage in mice subjected to middle cerebral artery occlusion (MCAO). MAIN METHODS: A mouse model of 4-hour MCAO was used to induce ischemic brain injury. Recombinant AT gamma was administered intravenously immediately after reperfusion at 4 h after MCAO. Infarct volume, neurological deficit, and regional cerebral blood flow (rCBF) were measured at 24 h after MCAO. To evaluate the effect of AT gamma on ischemic inflammation, we measured the number of Iba1-positive cells (marker of macrophage/microglial activation) and levels of proinflammatory cytokines. Further, we investigated the direct anti-inflammatory effects of rAT in the J774.1 cell line. KEY FINDINGS: Treatment with AT gamma (480 U/kg) reduced infarct volume and neurological deficit, and improved rCBF, in MCAO mice. Moreover, AT gamma treatment decreased the number of Iba1-positive cells and levels of proinflammatory cytokines. In vitro, treatment with thrombin significantly increased proinflammatory cytokine levels, which was significantly reduced by pretreatment with AT gamma. SIGNIFICANCE: Treatment with AT showed neuroprotective effects via anticoagulation actions, as well as direct anti-inflammatory effects on macrophage/microglial activation. These data suggest that AT may be a useful new therapeutic option for cerebral ischemia.


Assuntos
Antitrombinas/farmacologia , Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Antitrombinas/administração & dosagem , Isquemia Encefálica/patologia , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , Inflamação/tratamento farmacológico , Inflamação/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Recombinantes , Acidente Vascular Cerebral/patologia
18.
J Thromb Haemost ; 18(6): 1320-1323, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32329231

RESUMO

BACKGROUND: Antiviral drugs are administered in patients with severe COVID-19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS-CoV-2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. METHODS: All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C-trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. RESULTS: Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID-19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C-trough levels were 6.14 times higher during hospitalization than in the pre-hospitalization period. CONCLUSION: DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.


Assuntos
Antitrombinas/sangue , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Dabigatrana/sangue , Inibidores do Fator Xa/sangue , Pneumonia Viral/tratamento farmacológico , Pirazóis/sangue , Piridinas/sangue , Piridonas/sangue , Tiazóis/sangue , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Antivirais/administração & dosagem , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Darunavir/efeitos adversos , Interações Medicamentosas , Monitoramento de Medicamentos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Itália , Lopinavir/efeitos adversos , Masculino , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Medição de Risco , Fatores de Risco , Ritonavir/efeitos adversos , Índice de Gravidade de Doença , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos
19.
Cardiovasc Drugs Ther ; 34(4): 569-578, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32297024

RESUMO

BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in secondary stroke prevention in atrial fibrillation (AF) patients. METHODS: PubMed and Embase electronic databases were systematically searched from January 2009 to July 2019 for relevant randomized clinical trials and observational studies. A random-effects model was applied in the pooled analysis. RESULTS: A total of 14 studies (4 randomized clinical trials and 10 observational studies) were included. Based on the randomized clinical trials, compared with VKA use, the use of NOACs was associated with decreased risk of stroke and systemic embolism, major bleeding, and intracranial bleeding. Based on the observational studies, compared with VKAs, the subgroup analysis showed that dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran and apixaban were associated with a decreased risk of major bleeding. CONCLUSION: Based on current data, the use of NOACs is at least non-inferior to the use of VKAs in AF patients for secondary stroke prevention irrespective of NOAC type.


Assuntos
Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Dabigatrana/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Humanos , Hemorragias Intracranianas/induzido quimicamente , Estudos Observacionais como Assunto , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Piridonas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Tiazóis/administração & dosagem , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem
20.
Open Heart ; 7(1): e001202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32257246

RESUMO

Objective: We evaluated atrial fibrillation (AF) patients' perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications. Methods: The RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30-45 and 150-210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3. Results: The main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (p<0.001 for all) for treatment convenience (mean change V1 vs V2=20.72; SD=21.50; V1 vs V3=24.54; SD=22.85) and treatment satisfaction (mean change V1 vs V2=17.60; SD=18.76; V1 vs V3=21.04; SD=20.24). In cohort B, mean PACT-Q2 scores at V2 and V3 were significantly higher (p<0.001 for all) for dabigatran versus a VKA for treatment convenience (V2=18.38; SE =0.51; V3=23.34; SE=0.51) and satisfaction (V2=15.88; SE=0.39; V3=19.01; SE=0.41). Conclusions: Switching to dabigatran from long-term VKA therapy or newly initiated dabigatran is associated with improved patient treatment convenience and satisfaction compared with VKA therapy.


Assuntos
Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde , Satisfação do Paciente , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Dabigatrana/efeitos adversos , Substituição de Medicamentos , Europa (Continente) , Feminino , Hemorragia/induzido quimicamente , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Adulto Jovem
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