Luciano Moreira Baracioli

Safety and efficacy of prasugrel compared with clopidogrel in different regions of the world.

BACKGROUND Among patients with acute coronary syndrome (ACS), demographics, procedural characteristics and adjunctive medications differ globally. We examined whether there were differential effects of prasugrel compared with clopidogrel in the multinational TRITON-TIMI 38 study. METHODS We divided the enrollment into 5 pre-specified geographic regions. Patients were randomized to prasugrel or clopidogrel without regard to country of enrollment. End points are expressed as Kaplan-Meier failure estimates through 15 months. Heterogeneity was evaluated using Cox proportional hazards model. Additional sensitivity analyses were performed by dividing countries into categories based on the Human Development Index (HDI), which is a composite measure of social and economic development. RESULTS 13,608 patients were enrolled. Clinical characteristics including age, comorbidities, ACS presentation, stent types, and adjunctive medications differed broadly among regions. Despite these differences, no regional heterogeneity was observed with prasugrel compared to clopidogrel in the reduction of ischemic events (HR range: 0.76-0.87, p(interaction)>0.10 for each) and stent thrombosis (HR range: 0.34-0.72, p(interaction)>0.10 for each) or in the increased rate of non-CABG TIMI major bleeding (HR range: 1.16-1.76, p(interaction)>0.10 for each). There was a consistent trend in net clinical benefit (all cause death/MI/stroke/non-CABG TIMI major bleeding) favoring prasugrel (HR range: 0.81-0.97, p(interaction)>0.10 for each). Consistent results were also observed regarding the safety and efficacy of prasugrel compared with clopidogrel in both developed and developing countries. CONCLUSIONS Despite differences in patient demographics, procedural techniques and adjunctive medications, consistent reduction in ischemic events and increased bleeding were seen with prasugrel compared with clopidogrel throughout the world.

In Patients With Acute Myocardial Infarction, the Impact of Hyperglycemia as a Risk Factor for Mortality Is Not Homogeneous Across Age-Groups

OBJECTIVE To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), ≥50 and <60 (n = 477), ≥60 and <70 (n = 545), ≥70 and <80 (n = 495), and ≥80 years (n = 209). Hyperglycemia was defined as initial glucose ≥115 mg/dL. RESULTS The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1–5 were, respectively, 7.57 (P = 0.004), 3.21 (P = 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3–5. CONCLUSIONS The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients.

The role of invasive therapies in elderly patients with acute myocardial infarction.

INTRODUCTION: In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies - IT), especially in the context of long-term outcomes after hospital discharge. METHODS: We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were ≥70 years old (elderly group - EG), and 1040 were <70 years of age (younger group - YG); 1088 underwent IT during hospitalization, and the remaining 500 were treated medically (conservative therapy - CT). Patients were monitored either by visit or by phone at least once a year. A standard questionnaire was administered to all patients. The impact of IT was analyzed with both non-adjusted and adjusted models. RESULTS: By the end of the follow-up period, the survival rates for the IT and CT groups were, respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55, P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8% versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG (P=0.073) and 0.64 (P=0.001) in the EG. CONCLUSION: Long-term follow-up of patients with myocardial infarction revealed that IT during the in-hospital phase was at least as effective in elderly patients as in younger patients.

Diabetes subdiagnosticado e necrose miocárdica: preditores de hiperglicemia no infarto do miocárdio

BACKGROUND Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood. OBJECTIVE To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine); glucose metabolism factors [glycated hemoglobin (HbA1c); insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin); glycerides (triglycerides, VLDL and fatty acids); coagulation factors (factor VII, fibrinogen, plasminogen activator inhibitor-1); inflammation (high-sensitivity C reactive protein); and myocardial necrosis (CK-MB and troponin). Continuous variables were converted into degrees of relevance using fuzzy logic. RESULTS Significant correlation was observed between hyperglycemia and glucose metabolism (p < 0.001), lipoproteins (p = 0.03), and necrosis factors (p = 0.03). In the multivariate analysis, only glucose metabolism (OR = 4.3; CI = 2.1-68.9; and p < 0.001) and myocardial necrosis (OR = 22.5; CI = 2-253; and p = 0.012) showed independent and significant correlation. For the analysis of the influence of history of diabetes mellitus, a regression model including only patients without diabetes mellitus was developed, and the results did not change. Finally, in the model adjusted for age, gender, and clinical variables (history of diabetes mellitus, hypertension and dyslipidemia), three variables maintained a significant and independent association with hyperglycemia: glucose metabolism (OR = 24.1; CI = 4.8-122.1; and p < 0.001), myocardial necrosis (OR = 21.9; CI = 1.3-360.9; and p = 0.03), and history of DM (OR = 27; CI = 3.7-195.7; and p = 0.001). CONCLUSION Glucose metabolism and myocardial necrosis markers were the best predictors of hyperglycemia in patients with acute myocardial infarction.

Role of Oral Blockade of Platelet Glycoprotein IIb/IIIa on Neutrophil Activation in Patients with Acute Coronary Syndromes

Orbofiban is a unique antiplatelet agent that inhibits the binding of fibrinogen to gycoprotein (GP) IIb/IIIa integrin receptors and thus prevents platelet aggregation induced by various agents. However, recent studies indicate that treatment with orbofiban does not reduce the incidence of recurrent ischemic events. The mechanisms underlying the lack of benefit of orbofiban in patients with acute coronary syndromes are not completely clear. The purpose of this study was to characterize the effects of orbofiban on cellular activation (neutrophil superoxide generation) and surface expression of adhesion molecules of circulating neutrophils (CD18, CD11b, and L-selectin) and platelets (P-selectin and GP IIb/IIIa) in patients with acute coronary syndromes. After 5–7 days, orbifiban (50 mg BID) did not reduce PMN adhesion molecule expression and ex vivo-stimulated PMN superoxide generation—as was observed in the placebo group, without orbofiban. In contrast, orbofiban induced marked reductions in GP IIb/IIIa and P-selectin expressions after 5–7 days of treatment. The sustained neutrophil activation observed with orbofiban may have a role on the recurrent thrombotic events observed with orbofiban treatment in the OPUS-TIMI 16 trial.

Cirurgia de revascularização na fase aguda do infarto do miocárdio: análise dos fatores pré-operatórios preditores de mortalidade

OBJETIVO: Analisar os fatores pre-operatorios preditores de mortalidade, em pacientes submetidos a RM nos primeiros 30 dias apos infarto agudo do miocardio (IAM). METODOS: Entre 3/1998 e 7/2002, foram incluidos, consecutiva e prospectivamente, em um banco de dados, 753 pacientes com IAM, sendo que 135 (17,9%) foram submetidos a revascularizacao miocardica (RM) isolada e incluidos neste estudo. Estudaram-se os seguintes fatores prognosticos, atraves de analise multivariada: idade, sexo, diabete, historia de IAM, RM ou angioplastia (ATC), localizacao do IAM, IAM Q, uso de fibrinolitico, intervalo entre o IAM e a cirurgia, presenca de complicacoes no pre-operatorio. RESULTADOS: A mortalidade hospitalar global foi de 6,7%, variando de 12,5% nos pacientes portadores de complicacoes pre-operatorias a 1,4% naqueles sem complicacoes. Tiveram correlacao estatisticamente significante com a mortalidade pos-operatoria apenas historia previa de angioplastia (p=0,037) e choque cardiogenico (p=0,002). Em contrapartida, o uso de trombolitico na abordagem inicial do IAM apresentou correlacao negativa com a mortalidade (p=0,035). CONCLUSAO: A RM na fase aguda do IAM e um procedimento que apresenta mortalidade cirurgica distinta, na dependencia da condicao clinica pre-operatoria do paciente. Dentre os fatores analisados, a presenca de choque cardiogenico pre-operatorio e historia de angioplastia previa determinaram pior prognostico neste grupo de pacientes.

The bleeding risk score as a mortality predictor in patients with acute coronary syndrome

Background It is well known that the occurrence of bleeding increases in-hospital mortality in patients with acute coronary syndromes (ACS), and there is a good correlation between bleeding risk scores and bleeding incidence. However, the role of bleeding risk score as mortality predictor is poorly studied. Objective The main purpose of this paper was to analyze the role of bleeding risk score as in-hospital mortality predictor in a cohort of patients with ACS treated in a single cardiology tertiary center. Methods Out of 1,655 patients with ACS (547 with ST-elevation ACS and 1,118 with non-ST-elevation ACS), we calculated the ACUITY/HORIZONS bleeding score prospectively in 249 patients and retrospectively in the remaining 1,416. Mortality information and hemorrhagic complications were also obtained. Results Among the mean age of 64.3 ± 12.6 years, the mean bleeding score was 18 ± 7.7. The correlation between bleeding and mortality was highly significant (p < 0.001, OR = 5.296), as well as the correlation between bleeding score and in-hospital bleeding (p < 0.001, OR = 1.058), and between bleeding score and in-hospital mortality (adjusted OR = 1.121, p < 0.001, area under the ROC curve 0.753, p < 0.001). The adjusted OR and area under the ROC curve for the population with ST-elevation ACS were, respectively, 1.046 (p = 0.046) and 0.686 ± 0.040 (p < 0.001); for non-ST-elevation ACS the figures were, respectively, 1.150 (p < 0.001) and 0.769 ± 0.036 (p < 0.001). Conclusions Bleeding risk score is a very useful and highly reliable predictor of in-hospital mortality in a wide range of patients with acute coronary syndromes, especially in those with unstable angina or non-ST-elevation acute myocardial infarction.

Primary coronary angioplasty in a nonagenarian

A woman aged 98 years entered the tertiary hospital service with a picture of acute myocardial infarction of the extensive anterior wall, which began 4 hours earlier. Due to the large myocardial risk area suggested by the electrocardiogram, the patient was taken to the hemodynamics laboratory for the performance of emergency coronary arteriography, which revealed occlusion in the proximal third of the anterior descending artery. Primary angioplasty followed by stent grafting was successfully performed. The patient had a satisfactory evolution (Killip I) and was discharged from the hospital on the seventh postinfarction day. We discuss here aspects of thrombolysis and coronary percutaneous interventions in the aged.

SBC guidelines on unstable angina and non-ST-elevation myocardial infarction: executive summary.

Sources of Funding There were no external funding sources for this study. Study Association This study is not associated with any thesis or dissertation work.

Do Diabetic Patients with Acute Coronary Syndromes Have a Higher Threshold for Ischemic Pain

Background: Data from over 4 decades have reported a higher incidence of silent infarction among patients with diabetes mellitus (DM), but recent publications have shown conflicting results regarding the correlation between DM and presence of pain in patients with acute coronary syndromes (ACS). Objective: Our primary objective was to analyze the association between DM and precordial pain at hospital arrival. Secondary analyses evaluated the association between hyperglycemia and precordial pain at presentation, and the subgroup of patients presenting within 6 hours of symptom onset. Methods: We analyzed a prospectively designed registry of 3,544 patients with ACS admitted to a Coronary Care Unit of a tertiary hospital. We developed multivariable models to adjust for potential confounders. Results: Patients with precordial pain were less likely to have DM (30.3%) than those without pain (34.0%; unadjusted p = 0.029), but this difference was not significant after multivariable adjustment, for the global population (p = 0.84), and for subset of patients that presented within 6 hours from symptom onset (p = 0.51). In contrast, precordial pain was more likely among patients with hyperglycemia (41.2% vs 37.0% without hyperglycemia, p = 0.035) in the overall population and also among those who presented within 6 hours (41.6% vs. 32.3%, p = 0.001). Adjusted models showed an independent association between hyperglycemia and pain at presentation, especially among patients who presented within 6 hours (OR = 1.41, p = 0.008). Conclusion: In this non-selected ACS population, there was no correlation between DM and hospital presentation without precordial pain. Moreover, hyperglycemia correlated significantly with pain at presentation, especially in the population that arrived within 6 hours from symptom onset.