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1.
Medicine (Baltimore) ; 99(9): e19247, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118730

RESUMO

RATIONALE: The capsular warning syndrome (CWS) is a rare and special type of transient ischemic attacks (TIAs) syndrome. The pathophysiology of CWS is very complicate, and intracranial atherosclerotic stenosis (ICAS) is rare cause. Moreover, the effective and standard therapy has not yet been established. PATIENT CONCERNS: A 47-year-old man experienced repeated and exacerbated TIAs of right hemiparesis and dysarthria. Fourteen hours after the first episode of TIAs, he developed more severe right hemiparesis and dysarthria, the National Institute of Health Stroke Scale (NIHSS) score was 12 points, and did not recover in a long time. DIAGNOSIS: The computed tomography (CT) angiography displayed high stenosis in the M1 segment of the left middle cerebral artery. The patient was diagnosed as CWS with ICAS. INTERVENTIONS: Loading dose of clopidogrel and aspirin were started but were ineffective, then we used recombinant tissue plasminogen (r-tPA) for thrombolysis therapy after repeat CT scan that showed small acute infarcts in the right putamen and no bleeding. OUTCOMES: The patient was successfully treated by r-tPA intravenous thrombolysis after loading dose of dual-anti-platelet. He recovered rapidly, and the NIHSS score was 0 point, modified Rankin Scale score was 0 point, and Barthel Index score was 100 points at 3-month follow-up. LESSONS: r-tPA combined with loading dose of dual antiplatelet appears safe and effective in carefully selected CWS patients with ICAS. The collection of similar cases and further randomized controlled trial research would be desirable.


Assuntos
Fibrinolíticos/uso terapêutico , Arteriosclerose Intracraniana/tratamento farmacológico , Ataque Isquêmico Transitório/tratamento farmacológico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Clopidogrel/administração & dosagem , Clopidogrel/uso terapêutico , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Fibrinolíticos/administração & dosagem , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Síndrome , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X
2.
Expert Rev Cardiovasc Ther ; 18(1): 17-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32003297

RESUMO

Introduction: Platelets play a pivotal role in the occurrence of recurrent ischemic events in coronary artery disease patients who are treated with drug-eluting stents and are on dual antiplatelet therapy (DAPT).Areas covered: High platelet reactivity (HPR) to adenosine diphosphate during clopidogrel therapy is a strong predictor of post-stenting ischemic event occurrences. However, uniform use of potent P2Y12 receptors blockers to overcome HPR is associated with elevated bleeding risk. Selective de-escalation of P2Y12 receptor blocker therapy based on PFT in patients with acute coronary syndrome treated with stenting has been shown to be associated with a similar risk of ischemic event occurrence but with a reduced risk of bleeding. This review aims to discuss the role of PFT in guiding DAPT in patients treated with DES. We searched electronic databases from January 2000 to December 2019 for literatures evaluating the role of platelet function assessment after drug eluting stents.Expert opinion: Platelet function guided therapy improves patient outcomes by lessening bleeding and limiting the overuse of highly potent P2Y12 inhibitors. Interest in this area of de-escalation of therapy will likely grow as the consequences of bleeding are better recognized and the cost of healthcare gains greater focus.


Assuntos
Plaquetas/metabolismo , Stents Farmacológicos , Inibidores da Agregação de Plaquetas/administração & dosagem , Síndrome Coronariana Aguda/terapia , Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Quimioterapia Combinada , Stents Farmacológicos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Testes de Função Plaquetária , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem
3.
Medicine (Baltimore) ; 98(48): e18147, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770254

RESUMO

INTRODUCTION: Neurosyphilis is a chronic infection of the central nervous system that is commonly found in adult with long latency periods. Neurosyphilis-attributed deaths in young patients have grown exponentially in the past decade, yet there have been few studies on the early stages of neurosyphilis. PATIENT CONCERNS: A young male patient with syphilitic cerebral arteritis was evaluated in our clinic for the clinical signs of progressive ischemic stroke. DIAGNOSIS: The progression of syphilitic cerebral arteritis was observed through computed tomography imaging, magnetic resonance imaging, magnetic resonance angiogram, and transcranial color Doppler. The pathological changes and clinical outcomes were reviewed. In this specific case, the development of syphilitic cerebral arteritis was dynamic, continuous, and rapid. The pathogenesis was related to Heubner arteritis, in which the formation of a mural thrombus (MT) causes the severe obstruction of blood flow without complete occlusion, leading to an increased risk of infarction. In this patient, formation of the MT resulted in the infarction of the smaller vessels and narrowing of the larger vessels. The partial dislodgment of the MT from the arterial wall of the larger vessels occluded the smaller vessels, leading to infarction. INTERVENTIONS: Standard pharmacotherapy for the treatment of the cerebral infarction and a single course of penicillin were applied. OUTCOMES: Muscle strength was recovered. The Glasgow Coma Scale score was 15, whereas the NIH Stroke Scale score was 0. The increase in blood flow of the right MCA was accompanied by severe stenosis with compensation of the anterior communicating artery. In addition, moderate to severe stenosis of the right vertebral artery and the basilar artery was suspected. There was a possibility that the right posterior communicating artery was recruited for compensation. CONCLUSION: Progressive stroke was the initial symptom of the neurosyphilis. Disease progression is rapid and difficult to control with a single course of penicillin.


Assuntos
Atorvastatina/administração & dosagem , Infarto Encefálico , Clopidogrel/administração & dosagem , Edaravone/administração & dosagem , Neurossífilis , Vasculite do Sistema Nervoso Central , Adulto , Anticolesterolemiantes/administração & dosagem , Infarto Encefálico/diagnóstico , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/etiologia , Infarto Encefálico/fisiopatologia , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Força Muscular , Exame Neurológico/métodos , Fármacos Neuroprotetores/administração & dosagem , Neurossífilis/complicações , Neurossífilis/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana/métodos , Vasculite do Sistema Nervoso Central/diagnóstico , Vasculite do Sistema Nervoso Central/etiologia
4.
J Cardiothorac Surg ; 14(1): 202, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775803

RESUMO

BACKGROUND: Guidelines suggest that patients discontinue Clopidogrel at least 5 days prior to coronary artery bypass grafting (CABG). Those with acute coronary syndrome (ACS) are at high risk for myocardial infarction (MI) if not treated with dual antiplatelet therapy (DAPT). We sought to assess pre and post-operative outcomes of patients maintained on Clopidogrel and aspirin up to the time of surgery and compare them with those on aspirin alone. METHODS: From the cardiac surgery database, 240 patients were retrospectively registered between January and May 2017. There were 126 patients with ACS who underwent CABG on DAPT (Clopidogrel group [CG]) and 114 patients who underwent elective CABG on aspirin alone (control). The CG received intraoperative prophylactic platelet transfusion (PPT). Demographics, comorbidities, and laboratory data were prospectively entered at the time of surgery and were subsequently retrieved for analysis. Per and postoperative findings were identified and compared between both groups. RESULTS: The cohort consisted of 240 patients (mean age 61 years, 81.3% were male, SD ± 9.58). Patients in the CG were younger (Median 57 vs. 63, P-value 0.001), and with male predominance (86% versus 75%, P-value 0.028). In addition, they had less prevalence for diabetes and renal failure as compared to control (P-values 0.003, and 0.005, respectively). There were no significant differences between both groups in number of vessels grafts, duration of on-pump and aortic clamp. Hematologic laboratory data had also similar baseline values. The CG had similar bleeding rate, redo surgery and in-hospital death (P-values non-significant), however more infection and total hospital stay as compared to control (p-values 0.048 and 0.001). CONCLUSION: Patients who are at increased risk for MI can be maintained on DAPT up to the time of CABG because surgery is safe when patients are offered PPT.


Assuntos
Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Ponte de Artéria Coronária , Inibidores da Agregação de Plaquetas/administração & dosagem , Transfusão de Plaquetas , Cuidados Pré-Operatórios/métodos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Retrospectivos
5.
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
6.
Clin Drug Investig ; 39(10): 939-944, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267433

RESUMO

BACKGROUND: Aspirin-clopidogrel dual antiplatelet therapy and a proton-pump inhibitor are used worldwide to prevent thromboembolism and peptic ulceration in patients undergoing neurointervention. We performed VerifyNow assays (Accumetrics, San Diego, CA, USA) to retrospectively examine the relationship between the effectiveness of antiplatelet agents and different proton-pump inhibitor types. METHODS: Sixty-four patients with unruptured intracranial aneurysm scheduled for neurointervention received aspirin-clopidogrel dual antiplatelet therapy plus the proton-pump inhibitor lansoprazole (n = 34) or esomeprazole (n = 30). A low response to aspirin and clopidogrel was defined in terms of aspirin reaction units > 550 and P2Y12 reaction units ≥ 230, respectively, by VerifyNow assay. The characteristics, response to antiplatelet therapy, and clinical outcomes were compared in patients treated with lansoprazole or esomeprazole. RESULTS: The preoperative mean VerifyNow aspirin reaction units and P2Y12 reaction units were 466.0 ± 67.3 and 205.0 ± 67.6, respectively. The mean aspirin reaction unit value was 482.0 ± 64.1 in the lansoprazole group, and 461.5 ± 70.9 in the esomeprazole group (p = 0.77). The mean P2Y12 reaction unit was 220.0 ± 64.4 in the lansoprazole group, and 174.5 ± 65.0 in the esomeprazole group; there was a significant difference in the clopidogrel response of patient treated with lansoprazole or esomeprazole (p = 0.005). CONCLUSIONS: Our VerifyNow assay results suggest that when on lansoprazole fewer patients achieved the therapeutic goal and required extra therapy before neurointervention.


Assuntos
/métodos , Esomeprazol/administração & dosagem , Lansoprazol/administração & dosagem , Procedimentos Neurocirúrgicos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Estudos Retrospectivos , Tromboembolia/diagnóstico , Tromboembolia/prevenção & controle
7.
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
8.
Vasc Med ; 24(5): 422-430, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31339474

RESUMO

In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients with PAD to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. This post hoc analysis compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction (MI), or ischemic stroke) in patients with CKD (eGFR < 60 mL/min/1.73 m2) with those without CKD (eGFR ⩾ 60 mL/min/1.73 m2). The primary safety endpoint was thrombolysis in MI (TIMI) major bleeding. A total of 13,483 patients were included; 3332 (25%) had CKD, of whom 237 had stage 4/5 disease. Median follow-up was approximately 30 months. After statistical adjustment, patients with CKD had a higher rate of the primary endpoint compared with those without CKD (6.75 vs 3.72 events/100 patient-years; adjusted hazard ratio (HR) 1.45, 95% CI 1.30-1.63). CKD was not associated with increased risk of hospitalization for acute limb ischemia (ALI) (adjusted HR 0.96, 95% CI 0.69-1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66-1.28). CKD was not associated with a significantly increased risk of major bleeding (adjusted HR 1.21, 95% CI 0.89-1.64), but minor bleeding was significantly increased (adjusted HR 1.51, 95% CI 1.07-2.15). In conclusion, patients with PAD and CKD had higher rates of cardiovascular death, MI, and ischemic stroke, but similar rates of ALI, major amputation, and TIMI major bleeding when compared with patients without CKD. ClinicalTrials.gov Identifier: NCT01732822.


Assuntos
Clopidogrel/administração & dosagem , Taxa de Filtração Glomerular , Isquemia/tratamento farmacológico , Rim/fisiopatologia , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Insuficiência Renal Crônica/fisiopatologia , Ticagrelor/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Amputação , Isquemia Encefálica/mortalidade , Isquemia Encefálica/prevenção & controle , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Incidência , Isquemia/diagnóstico , Isquemia/mortalidade , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
9.
Rinsho Shinkeigaku ; 59(8): 525-529, 2019 Aug 29.
Artigo em Japonês | MEDLINE | ID: mdl-31341128

RESUMO

We herein experienced one patient with typical branch atheromatous disease (BAD) type infarction. Digital subtraction angiography (DSA) and MRI fusion imaging revealed the relationship between atheromatous plaque and perforating branches. A 66-year-old male presented acute onset of dysarthria, the left side hemiparesis and sensory disturbance. Diffusion-weighted MR imaging (DWI) showed the right pontine acute infarction. We started to treat with dual antiplatelet therapy. However, the left-side hemiparesis was worsening on 4 days after admission. DWI showed infarct growth and plaque imaging revealed the atheromatous plaque in the basilar artery. We fused DSA and MRI T2 weighted imaging (DSA-MR fusion imaging) to illustrate the relationship between the atheromatous plaque and the perforating branches. DSA-MR fusion imaging showed that the paramedian artery and the short circumferential artery ran around and into the pontine infarct lesion. Additionally, one of the paramedian arteries was occluded. Those neuroradiological findings coincided with the pathological concept of BAD. DSA-MR fusion imaging can prove the pathological concept of BAD.


Assuntos
Angiografia Digital , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Imagem de Tensor de Difusão , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Infarto Cerebral/terapia , Clopidogrel/administração & dosagem , Humanos , Masculino , Neuroimagem , Placa Aterosclerótica/terapia , Inibidores da Agregação de Plaquetas/administração & dosagem , Resultado do Tratamento
10.
J Invasive Cardiol ; 31(8): 235-238, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31303603

RESUMO

Dual-antiplatelet therapy is recommended for all patients with acute coronary syndromes (ACS), regardless of performance of revascularization. Ticagrelor (T) was shown to be superior to clopidogrel (C) in a large, randomized clinical trial, but data from real-world practice are lacking. We identified ACS patients from our institutional registry who underwent percutaneous coronary intervention and received one of the two drugs at hospital discharge based on physician preference. Among 1439 patients, there were 774 patients (53.8%) in the C group and 665 patients (46.2%) in the T group. T and C patients were similar except for a higher incidence of ST-elevation myocardial infarction (MI) and lower frequency of prior MI in the T group (P<.05 for both). The primary endpoint - 1-year all-cause death - occurred in 58 C patients and 48 T patients (6.9% vs 7.9%, respectively; P=.42). Sixty percent of these deaths (n = 62; 31 C and 31 T) were considered cardiovascular in nature based on chart review. By multivariable logistic regression model, only dialysis (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.50-4.64; P=.01), age (HR, 1.83; 95% CI, 1.49-2.24 per 10 years; P<.001), and prior heart failure (HR, 1.78; 95% CI, 1.12-2.82; P=.02) were independent predictors of 1-year death. Treatment with T was not a predictor of death (HR, 1.21; 95% CI, 0.81-1.82; P=.35) or cardiovascular death (HR, 1.18; 95% CI, 0.72-1.94; P=.52). Landmark analysis from day 10 showed similar results (HR, 1.13; 95% CI, 0.71-1.84; P=.59). Thus, we conclude that C and T have similar rates of 1-year all-cause mortality, which is predominantly affected by age, end-stage renal disease, and pre-existing heart failure.


Assuntos
Síndrome Coronariana Aguda/terapia , Clopidogrel/administração & dosagem , Intervenção Coronária Percutânea , Sistema de Registros , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Causas de Morte/tendências , Angiografia Coronária , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
Rinsho Shinkeigaku ; 59(7): 418-424, 2019 Jul 31.
Artigo em Japonês | MEDLINE | ID: mdl-31243247

RESUMO

A 76-year-old man, diagnosed with chronic myeloid leukemia in 2010, had been on nilotinib for 7 years. He presented with right hemiparesis in September 2017. He had no history of hypertension, diabetes, hyperlipidemia, heart disease, or smoking. Brain MRI revealed a border-zone infarction of the left cerebral hemisphere and a rapidly progressing severe left internal carotid artery (ICA) stenosis. He was initiated on clopidogrel and bosutinib instead of nilotinib. He presented with right hemiparesis once again in December 2017. Brain MRI revealed the border-zone infarction of the left cerebral hemisphere and a more progressed, severe bilateral ICA stenosis. A carotid ultrasound demonstrated iso-intense and concentrically narrowed ICA on both sides. Carotid artery stenting of the left ICA was performed in February 2018, and clopidogrel was replaced by cilostazol to provide a drug-induced rush. Carotid artery stenting of the right ICA was performed in June 2018 and cervical angiogram demonstrated that there were no residual artery stenoses in the bilateral stent. In recent years, several case reports suggest that tyrosine kinase inhibitors (TKIs) are associated with progressive artery stenosis and cause cerebral infarction. Brain imaging tests should be conducted to evaluate arterial stenosis progression for patients with a history of taking TKI when an arterial vascular event occurs.


Assuntos
Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Infarto Cerebral/induzido quimicamente , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Nitrilos/administração & dosagem , Nitrilos/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Administração Oral , Idoso , Artéria Carótida Interna , Estenose das Carótidas/induzido quimicamente , Estenose das Carótidas/cirurgia , Infarto Cerebral/diagnóstico por imagem , Clopidogrel/administração & dosagem , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Recidiva , Stents
12.
BMJ ; 365: l2222, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253632

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of standard term (12 months) or long term (>12 months) dual antiplatelet therapy (DAPT) versus short term (<6 months) DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Relevant studies published between June 1983 and April 2018 from Medline, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu. REVIEW METHODS: Randomised controlled trials comparing two of the three durations of DAPT (short term, standard term, and long term) after PCI with DES were included. The primary study outcomes were cardiac or non-cardiac death, all cause mortality, myocardial infarction, stent thrombosis, and all bleeding events. RESULTS: 17 studies (n=46 864) were included. Compared with short term DAPT, network meta-analysis showed that long term DAPT resulted in higher rates of major bleeding (odds ratio 1.78, 95% confidence interval 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92). No noticeable difference was observed in other primary endpoints. The sensitivity analysis revealed that the risks of non-cardiac death and bleeding were further increased for ≥18 months of DAPT compared with short term or standard term DAPT. In the subgroup analysis, long term DAPT led to higher all cause mortality than short term DAPT in patients implanted with newer-generation DES (1.99, 1.04 to 3.81); short term DAPT presented similar efficacy and safety to standard term DAPT with acute coronary syndrome (ACS) presentation and newer-generation DES placement. The heterogeneity of pooled trials was low, providing more confidence in the interpretation of results. CONCLUSIONS: In patients with all clinical presentations, compared with short term DAPT (clopidogrel), long term DAPT led to higher rates of major bleeding and non-cardiac death, and standard term DAPT was associated with an increased risk of any bleeding. For patients with ACS, short term DAPT presented similar efficacy and safety with standard term DAPT. For patients implanted with newer-generation DES, long term DAPT resulted in more all cause mortality than short term DAPT. Although the optimal duration of DAPT should take personal ischaemic and bleeding risks into account, this study suggested short term DAPT could be considered for most patients after PCI with DES, combining evidence from both direct and indirect comparisons. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099519.


Assuntos
Clopidogrel/uso terapêutico , Stents Farmacológicos/normas , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/mortalidade , Humanos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose/epidemiologia , Trombose/mortalidade
13.
Gastroenterol Hepatol ; 42(7): 423-428, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31155427

RESUMO

INTRODUCCIóN: Adherence to guidelines on the periendoscopic management of antiplatelet therapy (APT) has not been analyzed in detail. Our aim was to assess adherence to guidelines in patients referred to our Endoscopy Unit on a case-by-case basis, describing in detail the detected deviations and identifying areas of improvement. PATIENTS AND METHODS: Cross-sectional study of outpatients consecutively scheduled for an unsedated upper or lower gastrointestinal endoscopy between January and June 2015. Patients on anticoagulant therapy were excluded. RESULTS: 675 patients were evaluated, including 91 (13.5%) patients on APT [upper GI endoscopy 25 (27.5%), lower GI endoscopy 66 (72.5%)]. Contrary to the clinical guidelines, aspirin was discontinued in 25 of the 77 patients previously prescribed the drug (32.5%) but this modification was patient's own decision in 11 cases. Most of the apparent deviations in the management of clopidogrel and dual antiplatelet therapy (DAPT) were not true non-adherence cases. The Primary Care physician modified an APT prescribed by another physician in 8 of 9 cases (88.9%), always in cases with aspirin. No relationship was found between the endoscopic procedure's predicted risk of bleeding or the patient's thrombotic risk and modification of therapy. DISCUSSION: In many patients, the peri-procedural management of APT goes against current guidelines, but some of these inconsistencies cannot be considered true deviations from practice. Identified areas for improvement are increasing patient awareness about APT, disseminating the guidelines in Primary Care, and underscoring the significance of thrombotic risk related to APT withdrawal.


Assuntos
Endoscopia Gastrointestinal , Fidelidade a Diretrizes , Inibidores da Agregação de Plaquetas/administração & dosagem , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Colonoscopia , Contraindicações de Medicamentos , Estudos Transversais , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos
14.
Eur J Clin Pharmacol ; 75(8): 1059-1068, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31081522

RESUMO

PURPOSE: High on-treatment platelet reactivity (HTPR) after clopidogrel administration in patients with acute coronary syndrome (ACS) has been associated with an increased risk of adverse events. Our previous studies reported that half-dose ticagrelor provides a similar inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation as standard-dose ticagrelor, but half-dose of ticagrelor has not been studied in Chinese ACS patients with HTPR. This study aimed to compare the antiplatelet action of half-dose ticagrelor with high-dose clopidogrel in ACS patients with HTPR. METHODS: In this single-center randomized controlled trial, 80 (of 418 screened, 19.13%) ACS patients with HTPR while on clopidogrel were randomized to either half-dose ticagrelor (90 mg LD, then 45 mg twice daily) or high-dose clopidogrel (150 mg once daily). Platelet function was assessed by thromboelastography (TEG) and light transmission aggregometry (LTA), and adverse events were monitored throughout the study for 30 days. RESULTS: The ADP-induced platelet inhibition rate (IR) as measured by TEG was significantly higher for half-dose ticagrelor compared with high-dose clopidogrel (70.40% [61.10%-91.70%] vs. 44.25% [34.67%-79.07%], p = 0.001). The repeated HTPR rate was dramatically higher for high-dose clopidogrel compared with half-dose ticagrelor (6 of 32, 18.75% vs. 1 of 35, 2.85%; p = 0.04). No patients in either treatment group exhibited a major bleeding event or other adverse events. CONCLUSIONS: In ACS patients with HTPR, half-dose ticagrelor is more effective than high-dose clopidogrel in reducing platelet reactivity (NCT03062462).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , Clopidogrel/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Ticagrelor/efeitos adversos , Resultado do Tratamento
15.
Ann Thorac Surg ; 108(4): 1114-1120, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31039353

RESUMO

BACKGROUND: This study evaluated the impact of preoperative clopidogrel exposure on outcomes of coronary artery bypass grafting (CABG). METHODS: Patients undergoing isolated CABG from January 2010 to February 2018 at a single institution were included. Primary stratification was based on exposure to clopidogrel within 5 days of CABG. Primary outcomes included blood product transfusion and mediastinal reexploration for bleeding. Secondary outcomes included early and late mortality, major postoperative complications, and hospital readmissions. Multivariable Cox regression was used to evaluate the risk-adjusted impact of preoperative clopidogrel on post-CABG mortality. RESULTS: Isolated CABG was performed in 7048 patients, including 1240 (18%) who had received clopidogrel within 5 days. Patients who received preoperative clopidogrel had higher rates of transfusions (53.4% vs 40.3%, P < .001) and reoperation for bleeding (3.0% vs 2.0%, P = .02). Most postoperative complication rates were similar, although those exposed to clopidogrel had higher rates of postoperative stroke (2.3% vs 1.2%, P = .002) and prolonged ventilation (10.2% vs 7.1%, P < .001). Clopidogrel exposure did not impact unadjusted or risk-adjusted 30-day, 1-year, or 5-year mortality or readmission. Discontinuing clopidogrel for at least 3 days preoperatively mitigated but did not eliminate the increased risk of blood transfusions after CABG. CONCLUSIONS: CABG can be safely performed in patients with recent clopidogrel exposure with no increased risk of early or late mortality. However, CABG should be delayed for at least 5 days, if clinically feasible, to minimize transfusions and reoperation risk. In patients with more urgent indications, delaying CABG at least 3 days can mitigate but not eliminate the increased bleeding risk.


Assuntos
Clopidogrel/administração & dosagem , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Inibidores da Agregação de Plaquetas/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Idoso , Transfusão de Sangue , Estudos de Coortes , Doença da Artéria Coronariana/mortalidade , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Reoperação , Taxa de Sobrevida , Resultado do Tratamento
16.
PLoS One ; 14(5): e0216404, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31059535

RESUMO

BACKGROUND: Previous ischemic stroke is a predictor of recurrent ischemic stroke after an acute myocardial infarction (AMI). Dual antiplatelet therapy, including a P2Y12-inhibitor, is important in secondary prevention after AMI. Ticagrelor, a P2Y12-inhibitor, is more potent than the commonly used clopidogrel. Here, we evaluated the impact of ticagrelor on the risk of ischemic stroke following AMI in patients with previous ischemic stroke. METHODS: Data for patients with AMI that had a previous ischemic stroke were obtained from the Swedish Registry of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients were assigned to early and late cohorts, each covering a two-year time period before and after, respectively, the introduction of ticagrelor prescriptions (20 Dec 2011). Patients in the early cohort (n = 1633) were treated with clopidogrel (100%); those in the late cohort (n = 1642) were treated with either clopidogrel (66.3%) or ticagrelor (33.7%). We assessed the risk of ischemic stroke and intracranial bleeding over time with Kaplan-Meier analyses. We identified predictors of ischemic stroke with multivariable Cox regression analyses. RESULTS: Of 3275 patients, 311 experienced ischemic stroke after AMI. Cumulative Kaplan-Meier incidence estimates of ischemic stroke within one year after AMI were 12.1% versus 8.6% for the early and late cohorts, respectively (p<0.01). Intracranial bleeding incidences (1.2% versus 1.5%) were similar between the two cohorts. CONCLUSIONS: Ticagrelor introduction was associated with a lower rate of ischemic stroke, with no increase in intracranial bleeding, in an AMI population with a history of ischemic stroke.


Assuntos
Isquemia Encefálica , Infarto do Miocárdio , Sistema de Registros , Acidente Vascular Cerebral , Ticagrelor/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Isquemia Encefálica/prevenção & controle , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Taxa de Sobrevida , Ticagrelor/efeitos adversos
17.
Stroke ; 50(6): 1356-1363, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092165

RESUMO

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.


Assuntos
Clopidogrel/administração & dosagem , Hemorragias Intracranianas/prevenção & controle , Ataque Isquêmico Transitório/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/administração & dosagem , Idoso , Clopidogrel/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/etiologia , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Doença Arterial Periférica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Ticagrelor/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.
Heart Vessels ; 34(10): 1581-1588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30944971

RESUMO

Although it has been reported that prasugrel achieves stronger antiplatelet effect and fewer cardiovascular events compared to clopidogrel in Japanese patients, there are limited data comparing the safety between the 2 dose regimens. Data from 1031 consecutive patients with coronary artery disease undergoing PCI at 5 institutions from May 2014 to April 2016, who received aspirin plus either clopidogrel (619 patients) or prasugrel (412 patients), were retrospectively analyzed. The choice of clopidogrel or prasugrel was left to the operator's discretion. Adverse events were defined as a composite of bleeding, hepatopathy, leukopenia, thrombopenia, exanthema, and major adverse cardiovascular events (MACE). MACE was defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke. The average follow-up period was 143 days in the prasugrel group and 263 days in the clopidogrel group. Adverse events occurred in 34.5% of patients in the prasugrel group and in 28.6% in the clopidogrel group. Although the Kaplan-Meier curves showed lower survival rates from MACE, all-bleeding, major bleeding, minor bleeding, and adverse events, in the prasugrel group compared to the clopidogrel group (log rank test p = 0.009, p = 0.001, p = 0.012, p = 0.018, and p < 0.001, respectively), multivariate Cox-regression analyses determined prasugrel as a significant risk factor for all-bleeding, minor bleeding, and adverse events, but not for MACE and major bleeding events. Dual antiplatelet therapy with prasugrel was independently associated with minor bleeding events, but not with MACE and major bleeding events, compared to clopidogrel, after PCI in common clinical settings.


Assuntos
Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/terapia , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Feminino , Hemorragia/epidemiologia , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Inibidores da Agregação de Plaquetas/administração & dosagem , Cloridrato de Prasugrel/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
20.
Pharmacology ; 104(1-2): 21-27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970359

RESUMO

BACKGROUND: Combination therapy has been administered to patients with chronic or complex diseases due to its improved therapeutic effects compared with the results of monotherapy. Due to the pleiotropic effects of statins and antiplatelets, these drugs have been studied in combination with other drugs, but not all combinations exerted obvious beneficial effects compared with individual drugs. In this study, we aimed to compare the anti-inflammatory effects of 4 different combination therapies of statins and antiplatelets on the tumor necrosis factor (TNF)-mediated inflammation in vivo. METHODS: Mice were orally administered cilostazol plus pravastatin (CILOP) or cilostazol plus rosuvastatin (CILOR), clopidogrel plus pravastatin (CLOP), or clopidogrel plus rosuvastatin (CLOR); then, acute inflammation was induced by the injection of lipopolysaccharide (LPS) or TNF. Serum TNF levels, macrophage accumulation in the lesioned aortas, and mouse mortality were observed to be comparable to the anti-inflammatory effects of the combination therapies. RESULTS: In mice with LPS-induced inflammation, CILOP and CILOR substantially reduced macrophage infiltration of aortic lesions and the serum TNF levels compared with CLOP and CLOR. Moreover, among the 4 combinations, CILOP significantly improved the survival rate of mice with TNF-mediated acute lethal inflammation. CONCLUSIONS: The combination therapy comprising cilostazol and statins, particularly pravastatin, exerted the best anti-TNF effect compared with clopidogrel and statin therapy; thus, a suitable combination therapy, such as CILOP, can be a potential remedy to cure TNF-related diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inflamação/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Fator de Necrose Tumoral alfa/imunologia , Administração Oral , Animais , Cilostazol/administração & dosagem , Clopidogrel/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Pravastatina/administração & dosagem , Rosuvastatina Cálcica/administração & dosagem , Resultado do Tratamento
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