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Background Ticagrelor use during acute coronary syndromes demonstrated a decrease in all-cause mortality in the PLATO (Platelet Inhibition and Patient Outcomes) trial. This effect has been attributed to a non-platelet-derived improvement in endothelial function. The aim of this study was to determine differences in the number of endothelial progenitor cells and/or circulating endothelial cells found in peripheral blood in patients treated with either ticagrelor or clopidogrel during non-ST-segment-elevation myocardial infarction. Methods and Results In this multicenter, randomized study ( NCT 02244710), patients were considered for inclusion after non-ST-segment-elevation myocardial infarction whenever they were P2Y12-inhibitor naïve. Ticagrelor and clopidogrel were allocated at a 1:1 ratio. Blood samples for determining endothelial progenitor cells and circulating endothelial cells were extracted before the antiplatelet loading dose, 48 hours after presentation of index symptoms, and 1 month after the event. A multichannel cytometer was used for optimal cell characterization. A total of 96 patients fulfilled the inclusion criteria. Circulating endothelial cell levels corrected by white blood cells were as follows at baseline, 48 hours, and 1 month: 44 (28-64), 50 (33-63), and 38 (23-62) cells/mL, respectively, for clopidogrel and 38 (29-60), 45 (32-85), and 35 (24-71) cells/mL, respectively, for ticagrelor ( P=0.6). Endothelial progenitor cell levels were 29 (15-47), 27 (15-33), and 18 (10-25) cells/mL, respectively, for clopidogrel and 20 (11-33), 22 (12-32), and 18 (11-29) cells/mL, respectively, for ticagrelor ( P=0.9). No differences in intraindividual changes were found. Conclusions Patients treated with ticagrelor during non-ST-segment-elevation myocardial infarction, in comparison to clopidogrel, showed similar levels of endothelial progenitor cells and circulating endothelial cells. These data suggest that the endothelial protective effect mediated by ticagrelor is not related to bone marrow physiology modulation. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02244710.
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Clopidogrel/administração & dosagem , Células Progenitoras Endoteliais/metabolismo , Endotélio Vascular/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Ticagrelor/administração & dosagem , Vasodilatação/fisiologia , Idoso , Eletrocardiografia , Células Progenitoras Endoteliais/citologia , Feminino , Seguimentos , Humanos , Masculino , Infarto do Miocárdio sem Supradesnível do Segmento ST/metabolismo , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Inibidores da Agregação Plaquetária/administração & dosagem , Prognóstico , Método Simples-CegoRESUMO
Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy for patients presenting with ST-segment elevation myocardial infarction (STEMI) when it can be performed expeditiously and by experienced operators. In spite of excellent clinical results this technique is associated with longer delays than thrombolysis and this fact may nullify the benefit of selecting this therapeutic option. Several strategies have been proposed to decrease the temporal delays to deliver PPCI. Among them, prehospital diagnosis and direct transfer to the cath lab, by-passing the emergency department of hospitals, has emerged as an attractive way of diminishing delays. The purpose of this review is to address the effect of direct transfer on time delays and clinical events of patients with STEMI treated by PPCI.
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INTRODUCTION: A wide variability in the response to clopidogrel and magnitude of post-treatment platelet reactivity has been described. However, this has been demonstrated by light transmittance aggregometry, a method too laborious for daily practice. Point-of-care devices may overcome this limitation, but little is known on the predictive value of such measurements. Our objective was to determine the relationship between platelet reactivity and the incidence of myocardial damage following percutaneous coronary intervention (PCI) in patients with Non-ST-segment Elevation Acute Coronary Syndrome (NSTEACS). MATERIALS AND METHODS: This prospective study included 93 patients with NSTEACS and PCI. All patients received a loading dose of 300 mg of clopidogrel and 250 mg of aspirin. Myocardial damage was defined as any elevation above upper limit of normal or previous levels of troponin T, assessed every 6 h for at least 24 h following PCI. Platelet reactivity not related to clopidogrel (BASE reactivity), related to P2Y12 inhibition (P2Y12 reactivity) and inhibition of platelet aggregation (IPA) were assessed immediately pre-PCI with the VerifyNow device. RESULTS: Myocardial damage was detected in 60 patients (64.5%). Higher BASE reactivity was associated with myocardial damage (287.8+/-62.6 vs. 260+/-55.9 units, p=0.043) while a trend was found for P2Y12 reactivity (173.4+/-70.3 vs. 149.2+/-58.4 units, p=0.109). No relationship was detected for IPA. Multivariate logistic regression analysis confirmed that BASE reactivity (p=0.04) and P2Y12 reactivity (p=0.03) were independent predictors of myocardial damage. CONCLUSIONS: Platelet reactivity before PCI appears to be better predictor of myocardial damage than does response to clopidogrel.
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Síndrome Coronariana Aguda/sangue , Angioplastia Coronária com Balão/métodos , Plaquetas/citologia , Miocárdio/patologia , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Aspirina/uso terapêutico , Plaquetas/metabolismo , Clopidogrel , Feminino , Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2 , Receptores Purinérgicos P2Y12 , Ticlopidina/uso terapêuticoRESUMO
INTRODUCTION AND OBJECTIVES: Poor response to antiplatelet therapy has been associated with adverse long-term outcomes. The objective of this study is to assess the relationship between response to clopidogrel and post-treatment platelet reactivity (PPR) and 1-year major adverse cardiovascular events (MACE) in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). METHODS: Patients with NSTEACS undergoing early coronary angiography were enrolled in this prospective, observational study. The VerifyNow analyzer was used to measure clopidogrel response and PPR immediately before coronary angiography. RESULTS: Of the 179 patients included (97 percutaneous coronary intervention, 21 coronary artery bypass graft), 161 (90%) completed 1-year follow-up and 18 (11%) incurred MACE: 10 deaths, 6 myocardial infarctions, 2 strokes, 5 revascularizations. Lower response to clopidogrel (31 +/- 21% vs. 43 +/- 21%; P.049) and higher PPR (204 +/- 60 vs. 155 +/- 67 platelet reaction units [PRU]; p= 0.006) were significantly associated with MACE occurrence. Multivariate analysis confirmed PPR (OR per 10-unit increase: 1.12, 95%CI: 1.01-1.24; P.020) as an independent predictor of MACE. A PPR cut-off value of 175 PRU was associated with an adjusted OR for 1-year MACE occurrence of 3.9 (95%CI: 1.2-15.4; P.024). CONCLUSIONS: PPR predicts adverse long-term outcomes better than response to clopidogrel in patients with NSTEACS. Patients with PPR values above 175 PRU were identified as being at higher risk for adverse long-term events.
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Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/cirurgia , Plaquetas/fisiologia , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Testes de Função Plaquetária , Ticlopidina/análogos & derivados , Idoso , Angioplastia Coronária com Balão , Clopidogrel , Ponte de Artéria Coronária , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Resultado do TratamentoRESUMO
Introducción y objetivos. Una peor respuesta al tratamiento antiagregante está relacionada con la recurrencia de eventos clínicos. El objetivo de este estudio es valorar la relación entre la respuesta al clopidogrel y la reactividad plaquetaria post-tratamiento (RPP) con la recurrencia de eventos adversos cardiovasculares a 1 año en pacientes con síndrome coronario agudo sin elevación del ST (SCASEST). Métodos. Estudio observacional, prospectivo de la respuesta al clopidogrel y RPP (analizador VerifyNow®) inmediatamente antes de la coronariografía diagnóstica. Resultados. De 179 pacientes incluidos (97 con intervencionismo coronario y 21 con cirugía coronaria), 161 (90%) completaron seguimiento a 1 año y 18 (11%) sufrieron eventos: 10 muertes, 6 infartos agudos de miocardio no fatales, 2 accidentes cerebrovasculares y 5 nuevas revascularizaciones. Una peor respuesta al clopidogrel (31% ± 21% frente a 43% ± 21%; p = 0,049) y una mayor RPP (204 ± 60 frente a 155 ± 67 unidades de reactividad plaquetaria [URP]; p = 0,006) se asociaron significativamente con la aparición de eventos. El análisis multivariable confirmó la RPP (odds ratio [OR] por incremento de 10 URP = 1,12; intervalo de confianza [IC] del 95%, 1,01-1,24; p = 0,020) como predictor independiente de eventos adversos cardiovasculares mayores. Un punto de corte de RRP de 175 URP se asoció con OR ajustada = 3,9 (IC del 95%, 1,2-15,4; p = 0,024) para la aparición de eventos. Conclusiones. La RPP predice la aparición de eventos adversos a largo plazo mejor que la respuesta al clopidogrel en pacientes con SCASEST. Los pacientes con valores de RPP > 175 URP presentan mayor riesgo de sufrir eventos adversos
Introduction and objectives: Poor response to antiplatelet therapy has been associated with adverse long-term outcomes. The objective of this study is to assess the relationship between response to clopidogrel and post-treatment platelet reactivity (PPR) and 1-year major adverse cardiovascular events (MACE) in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Methods: Patients with NSTEACS undergoing early coronary angiography were enrolled in this prospective, observational study. The VerifyNow® analyzer was used to measure clopidogrel response and PPR immediately before coronary angiography. Results: Of the 179 patients included (97 percutaneous coronary intervention, 21 coronary artery bypass graft), 161 (90%) completed 1-year follow-up and 18 (11%) incurred MACE: 10 deaths, 6 myocardial infarctions, 2 strokes, 5 revascularizations. Lower response to clopidogrel (31 ± 21% vs. 43 ± 21%; P.049) and higher PPR (204 ± 60 vs. 155 ± 67 platelet reaction units [PRU]; p= 0.006) were significantly associated with MACE occurrence. Multivariate analysis confirmed PPR (OR per 10-unit increase: 1.12, 95%CI: 1.01-1.24; P.020) as an independent predictor of MACE. A PPR cut-off value of 175 PRU was associated with an adjusted OR for 1-year MACE occurrence of 3.9 (95%CI: 1.2-15.4; P.024). Conclusions: PPR predicts adverse long-term outcomes better than response to clopidogrel in patients with NSTEACS. Patients with PPR values above 175 PRU were identified as being at higher risk for adverse long-term events
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Humanos , Doença das Coronárias/complicações , Inibidores da Agregação Plaquetária/farmacocinética , Doença das Coronárias/tratamento farmacológico , Angiografia Coronária , Fatores de Risco , Ativação Plaquetária , Estudos Prospectivos , Testes de Função Plaquetária/tendências , Trombose Coronária/diagnósticoRESUMO
The interindividual response to antiplatelet treatment is considerable, with the magnitude of response often related to the appearance of clinical events after elective percutaneous coronary intervention (PCI). We investigated whether platelet aggregation inhibition (PAI) by early administration of abciximab would affect myocardial reperfusion outcomes observed after PCI in patients with acute ST-elevation myocardial infarction (STEMI). Consecutive patients with STEMI who were treated with PCI in our center were recruited (n = 56). Successful reperfusion was defined as a final Thrombolysis In Myocardial Infarction grade 3 flow, myocardial blush grade 2 or 3, and ST-segment resolution >50%. PAI grade was determined with the Ultegra Rapid Platelet Function Assay. Successful reperfusion criteria were observed in 34 patients (61%). There were 6 patients (11%) with a PAI value <80% and 34 (61%) with a PAI value > or =95%. Eight patients (36%) of those whose PAI was <95% had all the indicators of successful reperfusion compared with 26 patients (77%) whose PAI was > or =95% (p = 0.005). After adjusting for other variables (time from symptom onset to balloon, which was independently associated with myocardial reperfusion), the relation remained significant (p = 0.006). In conclusion, in patients with STEMI that was treated with direct PCI, higher platelet inhibition responses with early administration of abciximab were associated with better myocardial reperfusion outcomes.
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Anticorpos Monoclonais/farmacologia , Fragmentos Fab das Imunoglobulinas/farmacologia , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Inibidores da Agregação Plaquetária/farmacologia , Abciximab , Idoso , Anticorpos Monoclonais/administração & dosagem , Angiografia Coronária , Eletrocardiografia , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Inibidores da Agregação Plaquetária/administração & dosagem , Resultado do TratamentoRESUMO
Introducción. Los estudios que evalúan la seguridad de la ecocardiografía de estrés son escasos, con resultados discordantes y de series muy seleccionadas de centros con gran experiencia, difícilmente extrapolables. Objetivo. Conocer la seguridad de las diversas modalidades de ecocardiografía de estrés en nuestro medio. Método. Se analizaron retrospectivamente las complicaciones graves durante los ecocardiogramas de estrés practicadas en 29 hospitales de la península Ibérica, desde el inicio de su actividad hasta septiembre de 1999. En este período se habían realizado 22.105 ecocardiogramas, 10.975 de ejercicio, 2.969 con dobutamina a dosis bajas y 6.832 a dosis altas, 1.276 con dipiridamol, 41 con 'estimulación' y 12 con adenosina. Se consideró una complicación grave aquella que supuso riesgo vital o que precisó ingreso hospitalario. Resultados. Se registraron 26 complicaciones: una muerte, 3 fibrilaciones ventriculares, 10 taquicardias ventriculares sostenidas, 2 bloqueos auriculoventriculares completos, 6 infartos agudos de miocardio, 2 roturas de pared libre o tabique interventricular, un accidente isquémico transitorio y una hipotensión severa sintomática. Se presentó una complicación por cada 2.743 ecocardiografías de ejercicio, 1.231 de dipiridamol y 325 con dobutamina a dosis altas. No se presentó ninguna complicación con la dobutamina a dosis bajas. Se encontró relación entre la experiencia en ecocardiografía de estrés con dobutamina y la frecuencia de complicaciones. Tres complicaciones se presentaron después de haber terminado el test. Conclusiones. La ecocardiografía de estrés es una técnica segura, pero no inofensiva. La ecografía de estrés con ejercicio es la técnica más segura. Existe relación entre la experiencia y el número de complicaciones (AU)