Low platelet reactivity in patients with myocardial infarction treated with aspirin plus ticagrelor.

OBJECTIVE: Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin. METHODS: Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05. RESULTS: Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001). CONCLUSION: Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.

Low platelet reactivity in patients with myocardial infarction treated with aspirin plus ticagrelor

ABSTRACT Objective: Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin. Methods: Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05. Results: Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001). Conclusion: Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection.

In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection / Recomendações de suporte intensivo para pacientes graves com infecção suspeita ou confirmada pela COVID-19

ABSTRACT In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

RESUMO Em dezembro de 2019, uma série de pacientes com pneumonia grave foi identificada em Wuhan, província de Hubei, na China. Esses pacientes evoluíram para síndrome respiratória aguda grave e síndrome do desconforto respiratório agudo. Posteriormente, a COVID-19 foi atribuída a um novo betacoronavírus, o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Cerca de 20% dos pacientes com diagnóstico de COVID-19 desenvolvem formas graves da doença, incluindo insuficiência respiratória aguda hipoxêmica, síndrome respiratória aguda grave, síndrome do desconforto respiratório agudo e insuficiência renal aguda e requerem admissão em unidade de terapia intensiva. Não há nenhum ensaio clínico randomizado controlado que avalie potenciais tratamentos para pacientes com infecção confirmada pela COVID-19 no momento da publicação destas recomendações de tratamento. Dessa forma, essas recomendações são baseadas predominantemente na opinião de especialistas (grau de recomendação de nível C).

Acute management of unstable angina and non-ST segment elevation myocardial infarction.

Non-ST segment elevation coronary syndrome usually results from instability of an atherosclerotic plaque, with subsequent activation of platelets and several coagulation factors. Its treatment aims to reduce the ischemic pain, limiting myocardial damage and decreasing mortality. Several antiplatelet and anticoagulation agents have been proven useful, and new drugs have been added to the therapeutic armamentarium in the search for higher anti-ischemic efficacy and lower bleeding rates. Despite the advances, the mortality, infarction and readmission rates remain high.

Acute management of unstable angina and non-ST segment elevation myocardial infarction / Tratamento atual da síndrome coronária aguda sem supradesnivelamento do segmento ST

Non-ST segment elevation coronary syndrome usually results from instability of an atherosclerotic plaque, with subsequent activation of platelets and several coagulation factors. Its treatment aims to reduce the ischemic pain, limiting myocardial damage and decreasing mortality. Several antiplatelet and anticoagulation agents have been proven useful, and new drugs have been added to the therapeutic armamentarium in the search for higher anti-ischemic efficacy and lower bleeding rates. Despite the advances, the mortality, infarction and readmission rates remain high.

A síndrome coronária sem supradesnivelamento do ST geralmente resulta da instabilização de uma placa aterosclerótica, com subsequente ativação plaquetária e de diversos fatores de coagulação. O tratamento visa aliviar a dor isquêmica, limitar o dano miocárdico e diminuir a mortalidade. Diversos agentes antiagregantes e anticoagulantes provaram sua utilidade, e novas drogas passaram a compor o arsenal terapêutico, buscando maior eficácia anti-isquêmica e menores índices de sangramento. Apesar dos avanços, as taxas de mortalidade, infarto e reinternação ainda permanecem elevadas.

Heart Failure with Preserved Left Ventricular Ejection Fraction in Patients with Acute Myocardial Infarction / Insuficiência Cardíaca com Fração de Ejeção do Ventrículo Esquerdo Preservada em Pacientes com Infarto Agudo do Miocárdio

AbstractBackground:The prevalence and clinical outcomes of heart failure with preserved left ventricular ejection fraction after acute myocardial infarction have not been well elucidated.Objective:To analyze the prevalence of heart failure with preserved left ventricular ejection fraction in acute myocardial infarction and its association with mortality.Methods:Patients with acute myocardial infarction (n = 1,474) were prospectively included. Patients without heart failure (Killip score = 1), with heart failure with preserved left ventricular ejection fraction (Killip score > 1 and left ventricle ejection fraction ≥ 50%), and with systolic dysfunction (Killip score > 1 and left ventricle ejection fraction < 50%) on admission were compared. The association between systolic dysfunction with preserved left ventricular ejection fraction and in-hospital mortality was tested in adjusted models.Results:Among the patients included, 1,256 (85.2%) were admitted without heart failure (72% men, 67 ± 15 years), 78 (5.3%) with heart failure with preserved left ventricular ejection fraction (59% men, 76 ± 14 years), and 140 (9.5%) with systolic dysfunction (69% men, 76 ± 14 years), with mortality rates of 4.3%, 17.9%, and 27.1%, respectively (p < 0.001). Logistic regression (adjusted for sex, age, troponin, diabetes, and body mass index) demonstrated that heart failure with preserved left ventricular ejection fraction (OR 2.91; 95% CI 1.35–6.27; p = 0.006) and systolic dysfunction (OR 5.38; 95% CI 3.10 to 9.32; p < 0.001) were associated with in-hospital mortality.Conclusion:One-third of patients with acute myocardial infarction admitted with heart failure had preserved left ventricular ejection fraction. Although this subgroup exhibited more favorable outcomes than those with systolic dysfunction, this condition presented a three-fold higher risk of death than the group without heart failure. Patients with acute myocardial infarction and heart failure with preserved left ventricular ejection fraction encounter elevated short-term risk and require special attention and monitoring during hospitalization.

ResumoFundamento:A prevalência e os desfechos clínicos em pacientes com insuficiência cardíaca com fração de ejeção do ventrículo esquerdo preservada pós-infarto agudo do miocárdio ainda não foram bem elucidados.Objetivo:Analisar a prevalência de insuficiência cardíaca com fração de ejeção do ventrículo esquerdo preservada no infarto agudo do miocárdio e sua associação com a mortalidade.Métodos:Pacientes com infarto agudo do miocárdio (n = 1.474) foram incluídos prospectivamente. Pacientes admitidos sem insuficiência cardíaca (Killip = 1), com insuficiência cardíaca com fração de ejeção do ventrículo esquerdo preservada (Killip > 1 e fração de ejeção do ventrículo esquerdo ≥ 50%) e com insuficiência cardíaca sistólica (Killip > 1 e fração de ejeção do ventrículo esquerdo < 50%) foram comparados. A associação entre insuficiência cardíaca sistólica e com fração de ejeção do ventrículo esquerdo preservada, com a mortalidade hospitalar foi testada em modelos ajustados.Resultados:Dentre os incluídos, 1.256 (85,2%) pacientes foram admitidos sem insuficiência cardíaca (72% homens, 67 ± 15 anos), 78 (5,3%) com insuficiência cardíaca com fração de ejeção do ventrículo esquerdo preservada (59% homens, 76 ± 14 anos) e 140 (9,5%) com insuficiência cardíaca sistólica (69% homens, 76 ± 14 anos), com mortalidade, respectivamente, de 4,3; 17,9 e 27,1% (p < 0,001). A regressão logística (ajustada para sexo, idade, troponina, diabetes e índice de massa corporal) demonstrou que insuficiência cardíaca com fração de ejeção do ventrículo esquerdo preservada (odds ratio de 2,91; intervalo de confiança de 95% de 1,35-6,27; p = 0,006) e insuficiência cardíaca sistólica (odds ratio de 5,38; intervalo de confiança de 95% de 3,10-9,32; p < 0,001) se associaram à mortalidade intra-hospitalar.Conclusão:Um terço dos pacientes com infarto agudo do miocárdio admitidos com insuficiência cardíaca apresentou fração de ejeção do ventrículo esquerdo preservada. Apesar de esse subgrupo ter evolução mais favorável que os pacientes com insuficiência cardíaca sistólica, ele apresentou risco de morte três vezes maior do que o grupo sem insuficiência cardíaca. Pacientes com infarto agudo do miocárdio e insuficiência cardíaca com fração de ejeção do ventrículo esquerdo preservada apresentaram elevado risco em curto prazo e mereceram especial atenção e monitorização durante a internação hospitalar.

Heart failure with preserved left ventricular ejection fraction in patients with acute myocardial infarction.

BACKGROUND: The prevalence and clinical outcomes of heart failure with preserved left ventricular ejection fraction after acute myocardial infarction have not been well elucidated. OBJECTIVE: To analyze the prevalence of heart failure with preserved left ventricular ejection fraction in acute myocardial infarction and its association with mortality. METHODS: Patients with acute myocardial infarction (n = 1,474) were prospectively included. Patients without heart failure (Killip score = 1), with heart failure with preserved left ventricular ejection fraction (Killip score > 1 and left ventricle ejection fraction ≥ 50%), and with systolic dysfunction (Killip score > 1 and left ventricle ejection fraction < 50%) on admission were compared. The association between systolic dysfunction with preserved left ventricular ejection fraction and in-hospital mortality was tested in adjusted models. RESULTS: Among the patients included, 1,256 (85.2%) were admitted without heart failure (72% men, 67 ± 15 years), 78 (5.3%) with heart failure with preserved left ventricular ejection fraction (59% men, 76 ± 14 years), and 140 (9.5%) with systolic dysfunction (69% men, 76 ± 14 years), with mortality rates of 4.3%, 17.9%, and 27.1%, respectively (p < 0.001). Logistic regression (adjusted for sex, age, troponin, diabetes, and body mass index) demonstrated that heart failure with preserved left ventricular ejection fraction (OR 2.91; 95% CI 1.35-6.27; p = 0.006) and systolic dysfunction (OR 5.38; 95% CI 3.10 to 9.32; p < 0.001) were associated with in-hospital mortality. CONCLUSION: One-third of patients with acute myocardial infarction admitted with heart failure had preserved left ventricular ejection fraction. Although this subgroup exhibited more favorable outcomes than those with systolic dysfunction, this condition presented a three-fold higher risk of death than the group without heart failure. Patients with acute myocardial infarction and heart failure with preserved left ventricular ejection fraction encounter elevated short-term risk and require special attention and monitoring during hospitalization.

Effect of implementing an acute myocardial infarction guideline on quality indicators.

OBJECTIVE: To evaluate the compliance rates to quality of care indicators along the implementation of an acute myocardial infarction clinical practice guideline. METHODS: A clinical guideline for acute myocardial infarction was introduced on March 1st, 2005. Patients admitted for acute myocardial infarction from March 1st, 2005 to December 31st, 2012 (n=1,431) were compared to patients admitted for acute myocardial infarction before the implementation of the protocol (n=306). Compliance rates to quality of care indicators (ASA prescription on hospital admission and discharge, betablockers on discharge and door-to-balloon time) as well as the length of hospital stay and in-hospital mortality were compared before and after the implementation of the clinical guideline. RESULTS: The rates of ASA prescription on admission, on discharge and of betablockers were higher after guideline implementation: 99.6% versus 95.8% (p<0.001); 99.1% versus 95.8% (p<0.001); and 95.9% versus 81.7% (p<0.001), respectively. ASA prescription rate increased over time, reaching 100% from 2009 to 2012. Door-to-balloon time after versus before implementation was of 86(32) minutes versus 93(51) (p=0.20). The length of hospital stay after the implementation versus before was of 6(6) days versus 6(4) days (p=0.34). In-hospital mortality was 7.6% (before the implementation), 8.7% between 2005 and 2008, and 5.3% between 2009 and 2012, (p=0.04). CONCLUSION: The implementation of an acute myocardial infarction clinical practice guideline was associated with an increase in compliance to quality of care indicators.

Vascular calcification: pathophysiology and clinical implications.

Vascular calcification in coronary artery disease is gaining importance, both in scientific research and in clinical and imaging applications. The calcified plaque is considered the most relevant form of atherosclerosis within the coronary artery tree and is frequently a challenge for percutaneous intervention. Recent studies showed that plaque calcification is dynamic and is strictly related to the degree of vascular inflammation. Several inflammatory factors produced during the different phases of atherosclerosis induce the expression and activation of osteoblastic cells located within the arterial wall, which, in turn, promote the deposit of calcium. The vascular smooth muscle cells have an extraordinary capacity to undergo osteoblastic phenotypical differentiation. There is no doubt that the role of these factors, as well as the elements of genomics and proteomics, could be a vital strategic point in prevention and treatment. Within this context, we conducted an updating review on coronary calcification focused on pathophysiology, experimental models, and clinical implications of vascular calcification.

Efeito da implementação de um protocolo assistencial de infarto agudo do miocárdio sobre os indicadores de qualidade / Effect of implementing an acute myocardial infarction guideline on quality indicators

OBJETIVO: Avaliar a adesão aos indicadores de qualidade assistencial ao longo da implementação de um protocolo assistencial de infarto agudo do miocárdio. MÉTODOS: Em 1º de março de 2005 foi implementado o protocolo assistencial de infarto agudo do miocárdio. Foram selecionados pacientes admitidos de 1ºde março de 2005 a 31 de dezembro de 2012 (n=1.431). Para comparação, utilizamos os dados de pacientes admitidos por infarto na fase pré-protocolo (n=306). Comparamos a taxa de adesão aos indicadores (taxa de prescrição de AAS na admissão hospitalar e na alta hospitalar, betabloqueador na alta e tempo porta-balão) entre as fases pré e pós-implementação do protocolo, além de tempo de permanência hospitalar e mortalidade intra-hospitalar nas diferentes fases. RESULTADOS: As taxas de prescrição de AAS na admissão e na alta hospitalar, e de betabloqueador foram maiores na fase pós versus a pré-implementação do protocolo: 99,6% versus 95,8% (p<0,001); 99,1% versus 95,8% (p<0,001) e 95,9% versus 81,7% (p<0,001), respectivamente. A taxa de prescrição de AAS aumentou ao longo da implementação do protocolo, atingindo 100% de 2009 a 2012. O tempo porta-balão pós versus pré foi de 86(32) minutos versus 93(51), respectivamente (p=0,20). O tempo de permanência hospitalar foi semelhante na fase pré versus pós-protocolo: 6(6) dias versus 6(4) dias (p=0,34). A mortalidade intra-hospitalar foi de 7,6% no pré-protocolo, 8,7% entre 2005 e 2008 e 5,3% entre 2009 e 2012 (p=0,04). CONCLUSÃO: A implementação do protocolo assistencial refletiu-se na maior adesão aos indicadores de qualidade.

OBJECTIVE: To evaluate the compliance rates to quality of care indicators along the implementation of an acute myocardial infarction clinical practice guideline. METHODS: A clinical guideline for acute myocardial infarction was introduced on March 1st, 2005. Patients admitted for acute myocardial infarction from March 1st, 2005 to December 31st, 2012 (n=1,431) were compared to patients admitted for acute myocardial infarction before the implementation of the protocol (n=306). Compliance rates to quality of care indicators (ASA prescription on hospital admission and discharge, betablockers on discharge and door-to-balloon time) as well as the length of hospital stay and in-hospital mortality were compared before and after the implementation of the clinical guideline. RESULTS: The rates of ASA prescription on admission, on discharge and of betablockers were higher after guideline implementation: 99.6% versus 95.8% (p<0.001); 99.1% versus 95.8% (p<0.001); and 95.9% versus 81.7% (p<0.001), respectively. ASA prescription rate increased over time, reaching 100% from 2009 to 2012. Door-to-balloon time after versus before implementation was of 86(32) minutes versus 93(51) (p=0.20). The length of hospital stay after the implementation versus before was of 6(6) days versus 6(4) days (p=0.34). In-hospital mortality was 7.6% (before the implementation), 8.7% between 2005 and 2008, and 5.3% between 2009 and 2012, (p=0.04). CONCLUSION: The implementation of an acute myocardial infarction clinical practice guideline was associated with an increase in compliance to quality of care indicators.

Calcificação vascular: fisiopatologia e implicações clínicas / Vascular calcification: pathophysiology and clinical implications

A calcificação vascular na doença arterial coronária está ganhando importância, tanto em pesquisas científicas como em aplicações clínicas e de imagem. A placa calcificada é considerada a forma mais relevante de aterosclerose dentro da árvore arterial coronária e frequentemente apresenta um desafio para a intervenção percutânea. Estudos recentes têm demonstrado que a calcificação da placa é dinâmica e está estreitamente ligada ao grau de inflamação vascular. Vários fatores inflamatórios, produzidos durante as diferentes fases da aterosclerose, induzem a expressão e ativação de células osteoblásticas localizadas na parede arterial, que, por sua vez, promovem a deposição de cálcio. As células do músculo liso vascular possuem uma capacidade extraordinária de sofrer diferenciação fenotípica osteoblástica. Não há dúvida de que o papel desses fatores, bem como os elementos de genômica e proteômica, poderia ser um ponto estratégico fundamental na prevenção e no tratamento. Neste contexto, realizamos uma atualização sobre a calcificação coronária, com foco em fisiopatologia, modelos experimentais e implicações clínicas da calcificação vascular.

Vascular calcification in coronary artery disease is gaining importance, both in scientific research and in clinical and imaging applications. The calcified plaque is considered the most relevant form of atherosclerosis within the coronary artery tree and is frequently a challenge for percutaneous intervention. Recent studies showed that plaque calcification is dynamic and is strictly related to the degree of vascular inflammation. Several inflammatory factors produced during the different phases of atherosclerosis induce the expression and activation of osteoblastic cells located within the arterial wall, which, in turn, promote the deposit of calcium. The vascular smooth muscle cells have an extraordinary capacity to undergo osteoblastic phenotypical differentiation. There is no doubt that the role of these factors, as well as the elements of genomics and proteomics, could be a vital strategic point in prevention and treatment. Within this context, we conducted an updating review on coronary calcification focused on pathophysiology, experimental models, and clinical implications of vascular calcification.

Natriuretic peptides and long-term mortality in patients with severe aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The natriuretic peptides, brain natriuretic peptide (BNP) and its N-terminal prohormone (NT-proBNP), can be used as diagnostic and prognostic markers for aortic stenosis (AS). However, the association between BNP, NT-proBNP, and long-term clinical outcomes in patients with severe AS remains uncertain. METHODS: A total of 64 patients with severe AS was prospectively enrolled into the study, and underwent clinical and echocardiographic assessments at baseline. Blood samples were drawn for plasma BNP and NT-proBNP analyses. The primary outcome was death from any cause, through a six-year follow up period. Cox proportional hazards modeling was used to examine the association between natriuretic peptides and long-term mortality, adjusting for important clinical factors. RESULTS: During a mean period of 1,520 +/- 681 days, 51 patients (80%) were submitted to aortic valve replacement, and 13 patients (20%) were medically managed without surgical interventions. Mortality rates were 13.7% in the surgical group and 62% in the medically managed group (p < 0.001). Patients with higher plasma BNP (> 135 pg/ml) and NT-proBNP (> 1,150 pg/ml) levels at baseline had a greater risk of long-term mortality (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1-9.1; HR 4.3, 95% CI 1.4-13.5, respectively). After adjusting for important covariates, both BNP and NT-proBNP remained independently associated with long-term mortality (HR 2.9, 95% CI 1.5-5.7; HR 1.8, 95% CI 1.1-3.1, respectively). CONCLUSION: In patients with severe AS, plasma BNP and NT-proBNP levels were associated with long-term mortality. The use of these biomarkers to guide treatment might represent an interesting approach that deserves further evaluation.

Estudo da atividade inflamatória e plaquetária em pacientes com doença arterial coronária estável, submetidos a tratamentos com duas estratégias hipolipemiantes intensivas: sinvastatina 80mg e ezetimiba 10mg/sinvastatina 20mg / Study of the inflammatory and platelet activity in patients with stable coronary artery disease, treated with two antilipemic strategies: simvastatin 80 mg and ezetimibe 10 mg/simvastatin 20 mg

Em pacientes com doença arterial coronária (DAC) estável, não está claro se os efeitos da redução do colesterol sobre a inflamação, agregação plaquetária e células endoteliais progenitoras (CEPs) diferem entre duas estratégias hipolipemiantes: ezetimiba associada à sinvastatina em dose moderada e sinvastatina isolada em dose elevada. Objetivo: Avaliar os efeitos de sinvastatina em dose elevada comparada a ezetimiba associado à sinvastatina em dose moderada sobre a inflamação, agregação plaquetária e CEPs. Métodos e Resultados: Pacientes com DAC estável (n=83, 63 ± 9 anos, 48 homens), em uso de sinvastatina 20 mg, foram randomizados para tratamento com sinvastatina 80 mg (S80) ou ezetimiba 10 mg/sinvastatina 20 mg (E10/S20), por seis semanas. O perfil metabólico e lipídico, a proteína C-reativa (PCR), molécula de adesão intercelular solúvel (sICAM)-1, proteína quimiotática de monócitos (MCP)-1, interleucinas (IL) -1, -6 e -10, glicoproteína CD-40 ligante solúvel (sCD-40L), LDL oxidado (LDLox), células endoteliais progenitoras (CEPs) e a agregação plaquetária pelo platelet function analyzer (PFA)-100 foram avaliados antes e após o tratamento. Os níveis basais de lipídios, marcadores inflamatórios, CEPs e PFA-100 foram similares em ambos os grupos. Após o tratamento com S80 e E10/S20, ambos os grupos apresentaram: (1) Redução significante e similar de LDL-C (-23 + 30% vs -29 + 13%, respectivamente; p=0,46), Apo-B (-22 + 15% vs -18 + 17%, respectivamente; p=0,22) e LDLox (-18 + 47% vs -15 + 33%, respectivamente; p=0,65); (2) Redução modesta, similar e não significativa de PCR (-16% [IIQ: -42 - 7] vs -11% [IIQ= -37 26], respectivamente; p= 0,3). Nenhuma alteração significante foi encontrada nos marcadores inflamatórios restantes ou nas CEPs. (3) O PFA-100 elevou-se significativamente com E10/S20, mas não com S80 (27 + 43% vs 8 + 33%, respectivamente;p=0,02). Conclusão. Nossos dados demonstram que em pacientes com DAC estável: (1) Tanto S80 como E10/S20...

Among patients with stable coronary artery disease (CAD), it is not clear if the effects of cholesterol reduction on inflammation, platelet aggregation and endothelial progenitor cells (EPCs) differ between combined ezetimibe plus moderate-dose simvastatin and high-dose simvastatin alone. Objective: We sought to test the effects of a higher simvastatin dosage compared with combined treatment with ezetimibe plus a moderate simvastatin dose, on inflammation, platelet aggregation and EPCs. Methods and Results: CAD patients (n=83, 63 ± 9 years, 48 men), on simvastatin 20 mg, were randomly allocated to receive the combination ezetimibe 10 mg/simvastatin 20 mg (E10/S20) or simvastatin 80 mg (S80), for 6 weeks. Lipid profile, inflammatory markers (C-reactive protein [CRP], interleukin -1, -6 and -10, monocyte chemotactic protein (MCP)-1, soluble intercellular adhesion molecule (sICAM)-1, soluble CD-40 ligand [sCD-40L] and oxidized LDL [oxLDL]), platelet aggregation (platelet function analyzer [PFA]-100) and EPCs were determined before and after treatment. Baseline lipids, inflammatory markers and PFA-100 were similar in both groups. After treatment, S80 and E10/S20 patients presented: (1) significant and similar reductions on LDL-C (-23 + 30% vs -29 + 13%, respectively; p=0.46), Apo-B (-22 + 15% vs -18 + 17%, respectively; p=0.22) and oxLDL (-18 + 47% vs -15 + 33%, respectively; p=0.65), and (2) modest lowering on CRP (-16% [IIQ: - 42 - 7] vs -11% [IIQ= -37 26], respectively; p= 0.3). No significant changes were denoted among other inflammatory markers or EPCs. (3) PFA-100 increased significantly with E10/S20 but not with S80 (27 + 43% vs 8 + 33%, p=0.02). Conclusions. These data show that among stable CAD patients: (1) both E10/S20 and S80 are equally effective in reducing LDL-C, and have similar anti-inflammatory effects. (2) E10/S20 is more effective than S80 in inhibiting platelet aggregation...

Síndromes coronarianas agudas: tratamento e estratificação de risco / Acute coronary syndromes: treatment and risk stratification

JUSTIFICATIVA E OBJETIVOS: As síndromes coronarianas agudas são resultado da ruptura de uma placa coronariana instável, complicada pela formação de trombo intraluminal, embolização e graus variáveis de obstrução coronária. Pacientes com oclusão total de uma artéria coronária apresentam infarto agudo do miocárdio (IAM) com supradesnivelamento do segmento ST. Uma oclusão parcial do vaso pode resultar em IAM sem supradesnivelamento do segmento ST ou angina instável. As manifestações clínicas e as alterações eletrocardiográficas são componentes fundamentais para identificação dos pacientes portadores destas síndromes. A triagem rápida e eficaz desses pacientes, quanto à presença ou não do supradesnivelamento do segmento ST, é fundamental para a determinação da estratégia terapêutica a ser empregada. O objetivo deste estudo foi realizar uma revisão da literatura sobre as evidências atuais e as recomendações para avaliação e tratamento das síndromes coronarianas agudas. CONTEÚDO: Revisão da literatura, utilizando as bases eletrônicas de dados MedLine e LILACS, no período de janeiro de 1990 a setembro de 2007. CONCLUSÕES: A reperfusão da artéria responsável pelo infarto é a etapa fundamental no tratamento de pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST. A terapia trombolítica ou a intervenção coronariana percutânea são duas opções terapêuticas bem estabelecidas na literatura. Pacientes portadores de IAM sem supradesnivelamento do segmento ST ou angina instável necessitam de estratificação de risco precoce. Pacientes de alto risco devem ser submetidos à estratégia invasiva precoce, que consiste na realização do cateterismo cardíaco nas primeiras 24-48 horas do início dos sintomas.

BACKGROUND AND OBJECTIVES: Acute coronary syndromes result from a disruption of a vulnerable coronary plaque complicated by intraluminal thrombus formation, embolisation, and variable degrees of coronary obstruction. Patients with total occlusion may present with acute ST Elevation Myocardial Infarction (STEMI). Partial vessel obstruction may result in Non-ST-Elevation Acute Myocardial Infarction (NSTEMI) or unstable angina (UA). Clinical symptoms and electrocardiographic changes are the main components of identification of ACS. The rapid and effective triage of such patients regarding presence or absence of ST-segment elevation is critical to dictate further therapeutic strategies. The objective of this chapter was to review current evidence and recommendations for the evaluation and early treatment of acute coronary syndromes. CONTENTS: We performed a clinical review using the electronic databases MedLine and LILACS from January 1990 to September 2007. CONCLUSIONS: Reperfusion of the infarct-related artery is the cornerstone of therapy for STEMI. Fibrinolysis and percutaneous coronary intervention are both well established as effective options. Management of UA/NSTEMI patients requires early risk stratification. High-risk patients should undergo an early invasive strategy that consists in performance of cardiac catheterization in the first 24 to 48 hours of presentation.

Acute coronary syndromes: treatment and risk stratification. / Síndromes coronarianas agudas: tratamento e estratificação de risco.

BACKGROUND AND OBJECTIVES: Acute coronary syndromes result from a disruption of a vulnerable coronary plaque complicated by intraluminal thrombus formation, embolisation, and variable degrees of coronary obstruction. Patients with total occlusion may present with acute ST Elevation Myocardial Infarction (STEMI). Partial vessel obstruction may result in Non-ST-Elevation Acute Myocardial Infarction (NSTEMI) or unstable angina (UA). Clinical symptoms and electrocardiographic changes are the main components of identification of ACS. The rapid and effective triage of such patients regarding presence or absence of ST-segment elevation is critical to dictate further therapeutic strategies. The objective of this chapter was to review current evidence and recommendations for the evaluation and early treatment of acute coronary syndromes. CONTENTS: We performed a clinical review using the electronic databases MedLine and LILACS from January 1990 to September 2007. CONCLUSIONS: Reperfusion of the infarct-related artery is the cornerstone of therapy for STEMI. Fibrinolysis and percutaneous coronary intervention are both well established as effective options. Management of UA/NSTEMI patients requires early risk stratification. High-risk patients should undergo an early invasive strategy that consists in performance of cardiac catheterization in the first 24 to 48 hours of presentation.

[Acute myocardial infarction -- acute coronary syndrome with ST-segment elevation]. / Infarto agudo do miocárdio -- síndrome coronariana aguda com supradesnível do segmento ST.

Cardiovascular diseases continue to be the first cause of death in Brazil -- responsible for almost 32% of all deaths. In addition, they are the third major cause of admission in the country. Among them, acute myocardial infarction is still one of the major causes of morbidity and mortality. Despite of the last decade's therapeutic advances, acute myocardial infarction still shows remarkable rates of mortality, and great part of the patients do not receive the adequate treatment. The opening of the Coronary Care Units and the introduction of reperfusion treatment with fibrinolytics or primary angioplasty were fundamental to reduce mortality and complications related to myocardial infarction. Important beneficial effects to the current treatment include less ventricular dysfunction and better control of ventricular arrhythmias. The need of early reperfusion is crucial for the good prognosis after a myocardial infarction. The objective of this review is to emphasize the modern basic concepts of the pathophysiology, diagnosis and treatment of acute myocardial infarction, according to national and international guidelines.