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1.
Medicina (B Aires) ; 79(4): 315-321, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487255

RESUMO

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.


Assuntos
Aspirina/administração & dosagem , Benzodiazepinas/administração & dosagem , Clopidogrel/administração & dosagem , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Poliaminas/administração & dosagem , Quimioterapia Combinada , Humanos , Recidiva , Prevenção Secundária
2.
Am Surg ; 85(8): 871-876, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31560306

RESUMO

The aim of this study was to evaluate the impact of prehospital antiplatelet and/or anticoagulant (APAC) use on treatment and outcomes in patients with severe blunt chest injury. Patients with three or more rib fractures and a hospital length of stay (LOS) > three days admitted from 2014 to 2015 were included. Demographics, mortality, complications, injuries, hospital and ICU LOS, use of blood products, and thoracostomy were studied. Of 383 patients, 27.4 per cent were on APAC medication. Patients on APAC were older (P < 0.0001), had higher Glasgow Coma Score (P < 0.0001), and had lower Injury Severity Score (P < 0.0001) and total number of fractures (P = 0.0013) than the non-APAC group. APAC was not a predictor of mortality with or without age adjustment. In multiple linear regressions, APAC did not predict an increased LOS. APAC patients did not demonstrate an increase in admission diagnosis or complication of hemothorax, blood transfusions, tube thoracostomy, tracheostomy, LOS, or mortality rates. Similar findings are present in the subgroup of patients studied with high kinetic energy mechanism of injury. Our study does not support the perceived morbidity of APAC therapy in patients with severe blunt chest injury.


Assuntos
Anticoagulantes/administração & dosagem , Hemorragia/etiologia , Inibidores da Agregação de Plaquetas/administração & dosagem , Fraturas das Costelas/complicações , Ferimentos não Penetrantes/complicações , Fatores Etários , Idoso , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Feminino , Escala de Coma de Glasgow , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fraturas das Costelas/sangue , Fraturas das Costelas/terapia , Ferimentos não Penetrantes/sangue , Ferimentos não Penetrantes/terapia
4.
Vasc Endovascular Surg ; 53(7): 602-605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31272299

RESUMO

INTRODUCTION: Carotid angioplasty and stenting (CAS) represents an effective procedure for treating carotid artery disease. The acute in-stent thrombosis is an extremely rare complication of CAS especially when it occurs postprocedurally during the first 24 hours. Improper antiplatelet therapy or poor response to antiplatelet medications is known to be associated with a higher risk of in-stent thrombosis during early postprocedural period following a successful intervention. MATERIAL AND METHODS: A patient who experienced acute carotid in-stent thrombosis in early postprocedural period is described. He had been taking dual antiplatelet therapy for 2 weeks before undergoing a successful CAS. Moreover, pharmacogenetics studies showed the patient to be a clopidogrel ultrarapid metabolizer, which theoretically confers hyperresponsivity to medication. Alongside the report itself, a brief literature review of relevant sources pertinent to the case has been conducted. RESULTS: According to the available literature, this is the first case report describing an ultrarapid clopidogrel metabolizer who underwent an uneventful CAS but experienced acute carotid in-stent thrombosis in early postprocedural period. A rescue procedure included an endovascular intervention consisting of thrombectomy and local alteplase application, followed by postprocedural administration of intravenous eptifibatide. At discharge, patient's dual antiplatelet therapy included ticagrelor instead of clopidogrel. CONCLUSION: Acute carotid in-stent thrombosis is a highly unexpected complication of CAS and can occur despite ultrarapid clopidogrel metabolism trait.


Assuntos
Angioplastia com Balão/instrumentação , Estenose das Carótidas/terapia , Clopidogrel/metabolismo , Citocromo P-450 CYP2C19/metabolismo , Inibidores da Agregação de Plaquetas/metabolismo , Stents , Trombose/etiologia , Doença Aguda , Administração Intravenosa , Angiografia Digital , Angioplastia com Balão/efeitos adversos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Clopidogrel/administração & dosagem , Angiografia por Tomografia Computadorizada , Citocromo P-450 CYP2C19/genética , Substituição de Medicamentos , Eptifibatida/administração & dosagem , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Variantes Farmacogenômicos , Fenótipo , Inibidores da Agregação de Plaquetas/administração & dosagem , Fatores de Risco , Trombectomia , Trombose/diagnóstico por imagem , Trombose/terapia , Ticagrelor/administração & dosagem , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(30): e16586, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348297

RESUMO

RATIONALE: Acute myeloid leukemia (AML), in patients with coronary heart disease (CHD) and treated percutaneous coronary intervention (PCI), is rarely seen in clinic. There are few similar cases reported, and there are no evidence-based medicine guidelines for the treatment. PATIENT CONCERNS: A 52-year-old man was diagnosed with coronary atherosclerotic heart disease in November 2011, and received a stent placement in the left anterior descending coronary artery 1 year later. One day after the surgery, his laboratory tests showed pancytopenia. DIAGNOSES: Based on precise diagnosis of leukemia, namely cell morphology, immunology, cytogenetics, and molecular biological typing, the patient was diagnosed with AML-M2. INTERVENTIONS: The patient received idarubicin with cytarabine in 1st cycles, and single cytarabine regimen was used in 2nd and 3rd cycles for the accumulative toxicity of idarubicin in postinduction chemotherapy. Meanwhile, staged-treatment strategy was implemented by using antiplatelet drugs during different chemotherapy phases, and personalized pharmaceutical care on the basis of the recognition of potential adverse effects of chemotherapy regimen. OUTCOMES: Until now, the disease-free survival in the patient has been over 6 years, and he is still followed up in clinic. LESSONS: Although leukemia accompanied with coronary heart disease, even after receiving the coronary stenting therapy is rarely seen in clinic, the treatment with antiplatelet drugs for post chemotherapy patients with coronary disease is necessary. Clinical pharmacists are supposed to be more proficient in developing personalized drug treatment strategies, especially maintaining the balance between the effect and the risk in difficult and complex cases.


Assuntos
Doença das Coronárias/complicações , Doença das Coronárias/cirurgia , Leucemia Mieloide Aguda/complicações , Intervenção Coronária Percutânea/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Tromboembolia/prevenção & controle
6.
EuroIntervention ; 15(6): e551-e557, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31186218

RESUMO

AIMS: Early mortality after percutaneous coronary intervention (PCI) is relatively rare. Current risk prediction models for this event are outdated. We sought to derive a 30-day mortality risk score after PCI. METHODS AND RESULTS: The score was derived from a pooled database of 21 randomised clinical trials using a logistic regression model incorporating clinical and angiographic variables. The score was validated in a separate unrestricted study population, the Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents (ADAPT-DES) registry. Of 32,882 eligible patients, 75% had data for all 19 variables used for score derivation. The independent predictors of 30-day mortality were age, presentation with ACS, diabetes mellitus, use of first-generation drug-eluting stents, left main or left anterior descending artery lesion, prior myocardial infarction (MI), and suboptimal flow in the artery before or after PCI. The median [interquartile range] score in the derivation cohort was 5 [3, 6] and overall mortality was 0.49%, ranging from 0.08% to 1.64% with scores of 0-16. The 30-day mortality rate was approximately tenfold higher in patients with a score at or above versus below the median of 5 (0.86% versus 0.08%, p<0.0001). Discrimination in both cohorts was very good (C statistic=0.848 and 0.828, respectively), and calibration was satisfactory. CONCLUSIONS: A novel risk score incorporating eight readily available clinical and angiographic variables had high discrimination for 30-day death after PCI across a wide range of clinical scenarios.


Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco/métodos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
7.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
8.
N Engl J Med ; 380(20): 1906-1917, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31091372

RESUMO

BACKGROUND: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).


Assuntos
Antitrombinas/administração & dosagem , Dabigatrana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Antitrombinas/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Dabigatrana/efeitos adversos , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Embolia Intracraniana/tratamento farmacológico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Prevenção Secundária , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
10.
Lancet ; 393(10191): 2613-2623, 2019 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-31128924

RESUMO

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation.


Assuntos
Hemorragia Cerebral/epidemiologia , Inibidores da Agregação de Plaquetas/administração & dosagem , Acidente Vascular Cerebral/complicações , Doenças Vasculares/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Feminino , Humanos , Masculino , Cooperação do Paciente , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Reino Unido
11.
Ann Vasc Surg ; 59: 307.e7-307.e12, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075448

RESUMO

Thoracic aortic thrombus is a rare condition that can be a significant source of distal embolic events. This study details experience on the use of an endovascular technique for the management of thoracic aortic thrombus with a stent graft in 5 cases. Four of the cases were diagnosed with aortic arch thrombus, and 1 was diagnosed with distal descending aortic thrombus. All patients were females with age ranging from 44 to 71 years. Arterial embolism was the main clinical finding in most cases, which involved the upper extremities (n = 1) and cerebral embolism (n = 3), while 1 patient was asymptomatic. All 5 surgeries were considered technically successful with 0 perioperative all-cause mortality. Patients were discharged in a stable condition and were prescribed anticoagulant and antiplatelet medications. During follow-up visits, there were no instances of stent-graft failure or collapse, leak, or distal migration. Furthermore, there was complete resolution of the intraluminal thrombus, and all patients were asymptomatic.


Assuntos
Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Trombose/cirurgia , Adulto , Idoso , Anticoagulantes/administração & dosagem , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/fisiopatologia , Aortografia/métodos , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Estudos Retrospectivos , Stents , Trombose/diagnóstico por imagem , Trombose/fisiopatologia , Resultado do Tratamento
12.
Herz ; 44(4): 365-378, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31087108

RESUMO

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary intervention and also after acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina pectoris); however, DAPT is not sufficient for stroke prevention in atrial fibrillation (SPAF). For SPAF, oral anticoagulation (OAC) with vitamin K antagonists (VKA) or non-vitamin K-dependent anticoagulants (NOAC) is required. If a patient who is receiving anticoagulants for SPAF, requires a coronary intervention, triple therapy consisting of OAC plus DAPT is given, at least for a limited time following the procedure. This article reviews the current data from studies testing strategies with NOACs plus one or two antiplatelet substances in comparison to triple therapy with VKA.


Assuntos
Anticoagulantes , Fibrilação Atrial , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas , Síndrome Coronariana Aguda/terapia , Administração Oral , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Quimioterapia Combinada , Humanos , Inibidores da Agregação de Plaquetas/administração & dosagem
13.
J Stroke Cerebrovasc Dis ; 28(6): e64-e65, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30935806

RESUMO

Ischaemic stroke secondary to isolated internal carotid artery thrombus without risk factors is uncommon. A 55-year-old woman presented to the acute stroke unit with acute right middle cerebral artery territory infarction secondary to right internal carotid artery occlusion. There were no risk factors for cerebrovascular disease, but mediastinal imaging showed the presence of a large retrosternal goitre which was displacing the mediastinal structures including the brachiocephalic and common carotid artery. Intraluminal thrombus is visible in the displaced innominate artery and is the underlying cause for the stroke in our patient. This case highlights the importance of appropriate imaging of the mediastinum in cases with thyroid goitre.


Assuntos
Artéria Carótida Interna , Estenose das Carótidas/etiologia , Bócio/complicações , Infarto da Artéria Cerebral Média/etiologia , Tromboembolia/etiologia , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Tratamento Conservador , Feminino , Bócio/diagnóstico por imagem , Bócio/terapia , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/terapia , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Tromboembolia/diagnóstico por imagem , Tromboembolia/terapia , Resultado do Tratamento
14.
Ann Vasc Surg ; 59: 244-247, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31009712

RESUMO

BACKGROUND: Inflammation and endothelial dysfunction are implicated in the onset of atherosclerosis. Inflammasome activation takes part in the pathogenesis of the atherosclerotic disease. This study investigated the influence of platelet inflammatory inhibition on the transcription of intracitosolic nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP-1) inflammasome in endothelial cells. METHODS: This experimental study enrolled 10 healthy volunteers with no cardiovascular risk factors and normal results on vascular examination. They received low doses of aspirin (100 mg/day) for seven days. A venous blood sample was collected in all subjects before aspirin intake and after the experimental week. Human aortic endothelial cell (HAEC) cultures were exposed to baseline plasma and plasma from subjects after aspirin intake. NLRP-1 gene expression was analyzed in these cultures. RESULTS: HAEC cultures that were exposed to plasma from subjects at baseline showed higher expression of NLRP-1 than HAECs exposed to plasma of healthy volunteers after one week on salicilate intake (relative quantification, 1.077 ± 0.05 vs. 1.002 ± 0.06; odds ratio, 1.8; 95 confidence interval, 1.1-2.9; P < 0.01). CONCLUSIONS: Data observed in the our study indicate that in HAECs, the intracytosolic NLRP-1 expression is attenuated by the auto/paracrine platelet inhibition by aspirin, without direct platelet-endothelial cell interaction.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Anti-Inflamatórios/administração & dosagem , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Inflamassomos/antagonistas & inibidores , Inibidores da Agregação de Plaquetas/administração & dosagem , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Plaquetas/metabolismo , Comunicação Celular/efeitos dos fármacos , Células Cultivadas , Estudos Clínicos como Assunto , Regulação para Baixo , Células Endoteliais/metabolismo , Voluntários Saudáveis , Humanos , Inflamassomos/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Wien Klin Wochenschr ; 131(Suppl 1): 139-140, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30980156

RESUMO

Acute thrombotic complications as a key feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to cardiovascular morbidity and mortality in diabetic patients. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in diabetic patients according to current scientific evidence.


Assuntos
Angiopatias Diabéticas/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Trombose , Áustria , Plaquetas , Angiopatias Diabéticas/prevenção & controle , Humanos , Agregação Plaquetária , Guias de Prática Clínica como Assunto , Trombose/tratamento farmacológico , Trombose/prevenção & controle
16.
Artigo em Alemão | MEDLINE | ID: mdl-31013528

RESUMO

In 2018, two active pharmaceutical ingredients were released on the German market for small animals: the ectoparasiticide of the isoxazoline group Lotilaner (Credelio®) and the opioid analgesic Tramadol (Tralieve®). Two established veterinary active pharmaceutical ingredients became available for additional species: the nonsteroidal anti-inflammatory drug Meloxicam (Metacam®) from the oxicam group for guinea pigs and the inhalant anesthetic Sevoflurane (Sevoflo®) from the group of halogenated hydrocarbon compounds, which has additionally been authorized for cats. With the combination of Benzylpenicillin-Benzathine and Benzylpenicillin-Procaine, one temporarily non-available combination of active ingredients was reapproved in new drugs. Additionally, one drug with a new pharmaceutical form and one drug with a higher content of the active ingredient have been launched on the market for small animals.


Assuntos
Antibacterianos/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Antiparasitários/uso terapêutico , Inibidores da Agregação de Plaquetas/administração & dosagem , Animais , Gatos , Dexametasona/administração & dosagem , Cães , Ectoparasitoses/tratamento farmacológico , Ectoparasitoses/veterinária , Cobaias , Injeções/veterinária , Isoxazóis/administração & dosagem , Isoxazóis/uso terapêutico , Meloxicam/uso terapêutico , Penicilina G Benzatina/administração & dosagem , Penicilina G Procaína/administração & dosagem , Sevoflurano/administração & dosagem , Soluções , Suspensões , Comprimidos , Telmisartan/administração & dosagem , Tramadol/administração & dosagem , Tramadol/uso terapêutico
17.
Minerva Cardioangiol ; 67(2): 109-114, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30964246

RESUMO

BACKGROUND: The aim of this study is to evaluate the use of Aspirin, Pycnogenol®, ticlopidine, and sulodexide to reduce the incidence of new RTV (retinal vein thrombosis) after a first episode. Pycnogenol® is an anti-inflammatory, anti-edema, mild antiplatelet-antithrombotic agent. METHODS: The registry study evaluated the number of repeated episodes of RVT in 12 months. Possible managements were: standard management (SM); SM + Aspirin (100 mg/once day; if there were no tolerability problems); SM + Pycnogenol (100 mg/day); SM and ticlopidine (200 mg/day); SM + sulodexide (500 ULS/day). The number of subjects age and sex, distribution, the percent of smokers, the vision were comparable at inclusion. RESULTS: 307 subjects completed the study, 44 in the SM group, 90 in the Pycnogenol® group, 90 in the aspirin group, 45 in the ticlopidine group and 38 in the sulodexide group. At 12 months, recurrent RVT was documented in 22.7% of controls (SM), 3.3% of Pycnogenol® subjects (P<0.05 vs. SM; 19.4% difference). There were RVTs in 15.5% subjects using Aspirin (-7.2% vs. SM). Ticlopidine also reduced (P<0.05) the incidence of RVT in comparison with SM (-9.1%). Sulodexide reduced the occurrence of new RVT (-9.5% vs. SM). Edema was better controlled with the supplement than with all other treatments (P<0.05) (edema present in only 5.5% of the Pycnogenol® subjects). Pycnogenol® had a very good tolerability and safety profile (no patient had to stop treatment). CONCLUSIONS: Pycnogenol® is the only product able to control edema and this may reduce the incidence of recurrent RVT. This retrospective registry indicates that Aspirin, Pycnogenol®, ticlopidine an sulodexide reduce recurrent RVT without side effects. Larger studies should be planned to involve a wider range of conditions, diseases and risk factors associated with RVT and to its recurrence.


Assuntos
Fibrinolíticos/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Oclusão da Veia Retiniana/prevenção & controle , Adulto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Flavonoides/administração & dosagem , Flavonoides/efeitos adversos , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos
18.
Am J Vet Res ; 80(5): 505-512, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31034271

RESUMO

OBJECTIVE: To determine pharmacokinetics and pharmacodynamics after oral administration of a single dose of clopidogrel to horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Blood samples were collected before and at various times up to 24 hours after oral administration of clopidogrel (2 mg/kg). Reactivity of platelets from each blood sample was determined by optical aggregometry and phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Concentrations of clopidogrel and the clopidogrel active metabolite derivative (CAMD) were measured in each blood sample by use of liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined with a noncompartmental model. RESULTS: Compared with results for preadministration samples, platelet aggregation in response to 12.5µM ADP decreased significantly within 4 hours after clopidogrel administration for 5 of 6 horses. After 24 hours, platelet aggregation was identical to that measured before administration. Platelet aggregation in response to 25µM ADP was identical between samples obtained before and after administration. Phosphorylation of VASP in response to ADP (20µM) and prostaglandin E1 (3.3µM) was also unchanged by administration of clopidogrel. Time to maximum concentration of clopidogrel and CAMD was 0.54 and 0.71 hours, respectively, and calculated terminal-phase half-life of clopidogrel and CAMD was 1.81 and 0.97 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Clopidogrel or CAMD caused competitive inhibition of ADP-induced platelet aggregation during the first 24 hours after clopidogrel administration. Because CAMD was rapidly eliminated from horses, clopidogrel administration may be needed more frequently than in other species in which clopidogrel causes irreversible platelet inhibition. (Am J Vet Res 2019;80:505-512).


Assuntos
Plaquetas/efeitos dos fármacos , Clopidogrel/farmacocinética , Cavalos/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/farmacocinética , Difosfato de Adenosina/farmacologia , Administração Oral , Animais , Área Sob a Curva , Plaquetas/metabolismo , Moléculas de Adesão Celular/metabolismo , Clopidogrel/administração & dosagem , Feminino , Masculino , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Fosforilação , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/administração & dosagem
19.
EuroIntervention ; 15(6): e513-e521, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31012853

RESUMO

AIMS: A guided de-escalation of P2Y12 inhibitor treatment is considered an alternative treatment strategy in ACS patients undergoing PCI. However, the safety and efficacy of this strategy may differ in diabetic vs non-diabetic patients. The aim of this study was to compare the outcomes of platelet function testing (PFT)-guided de-escalation of dual antiplatelet therapy (DAPT) in ACS patients with and without diabetes mellitus. METHODS AND RESULTS: The TROPICAL-ACS trial randomised 2,610 biomarker-positive ACS patients 1:1 to either standard treatment with prasugrel for 12 months (control group) or PFT-guided DAPT de-escalation. The association and interaction of diabetes on clinical endpoints across treatment groups and on platelet reactivity was investigated. In diabetic patients (n=527, 20.2%), the overall event rates were high and the one-year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke or bleeding ≥grade 2) did not differ between guided de-escalation and control group patients (12.5% vs 10.8%; HR 1.17, 95% CI: 0.71-1.93, p=0.55). In non-diabetic patients (n=2,083, 79.8%), the one-year incidence of the primary endpoint was lower in the guided de-escalation vs control group (6.1% vs 8.5%; HR 0.71, 95% CI: 0.52-0.99, p=0.04, pint=0.10). Diabetic patients showed higher platelet reactivity levels in both control (=on prasugrel, p=0.01) and guided de-escalation group (=on clopidogrel, p=0.005) patients. CONCLUSIONS: Although diabetic status did not significantly interfere with the treatment effects of guided DAPT de-escalation, our results suggest that this approach might be safe and effective in non-diabetic patients. Further investigation is definitely warranted in diabetic patients.


Assuntos
Síndrome Coronariana Aguda , Diabetes Mellitus , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Cloridrato de Prasugrel/administração & dosagem , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Cloridrato de Prasugrel/efeitos adversos , Resultado do Tratamento
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 217: 176-181, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30933782

RESUMO

The morbidity of coronary heart disease (CHD) with high risks has been rising in recent years. A novel and noninvasive method based on surface-enhanced Raman spectroscopy (SERS) was proposed by Yang et al. (Analyst 143: 2235, 2018) to prospectively diagnose the arterial blockage by detecting platelet-derived growth factor-BB (PDGF-BB) in urine. Clinically, anti-platelet drugs (such as aspirin, statins and clopidogrel) are often used for ordinary CHD patients or patients with percutaneous coronary intervention (PCI). Therefore, whether the previous developed method can be applied to the CHD patients on long-term medication (more than 6 months) or post-PCI patients was investigated here. Firstly, urine samples of 13 CHD patients on long-term medication (aspirin, rosuvastatin, clopidogrel bisulfate) and 13 post-PCI patients were measured by the proposed method. Clinical data of coronary angiography results provided by Xin Hua Hospital and Yangpu District Central Hospital Antu Branch revealed that these 26 patients were with serious arterial blockage, however, characteristic Raman peak at 1509 cm-1 attributed to PDGF-BB was not observed in the SERS spectra of these 26 patients. In addition, an eight-day follow-up investigation was performed on a CHD patient with PCI three years ago and on long-term medication. It was found that the Raman peak at 1509 cm-1 could be only observed in the third and fourth day after suspending the drugs. Furthermore, SERS spectra of mixed solutions of PDGF-BB and aspirin, rosuvastatin, mixed solutions of these two drugs and clopidogrel bisulfate were analyzed. The Raman peak at 1509 cm-1 was not found in all these spectra, it indicated that all the three kinds of drugs could influence on the SERS signal of PDGF-BB. Therefore, the previous developed method is not suitable for CHD patients on long-term medication and post-PCI patients.


Assuntos
Becaplermina/urina , Doença das Coronárias/diagnóstico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Análise Espectral Raman/métodos , Aspirina/administração & dosagem , Becaplermina/efeitos dos fármacos , Clopidogrel/administração & dosagem , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/urina , Humanos , Estudos Prospectivos
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