Antonio Eduardo Pereira Pesaro

Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin

BACKGROUND In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone. OBJECTIVE We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10mg/simvastatin 20mg (E10/S20) with simvastatin 80 mg (S80). METHODS AND RESULTS CAD patients (n=83, 63 ± 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 ± 13% vs. 28 ± 30%, p=0.46), apo-B (18 ± 17% vs. 22 ± 15%, p=0.22) and oxidized LDL (15 ± 33% vs. 18 ± 47%, p=0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 ± 43% vs. 8 ± 33%, p=0.02). CONCLUSIONS These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4× less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80.

Calcificação vascular: fisiopatologia e implicações clínicas

ABSTRACT 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.

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 decades 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.

Coronary artery bypass surgery, angioplasty and long term anti-platelet treatment in a type B hemophilia patient

Hemophilia patients usually have a lower incidence of coronary artery disease (CAD).1 However, as their life expectancy increases so does the incidence of CAD. Anti-platelet drugs, diagnostic coronary catheterization, angioplasty and coronary artery bypass surgery (CABG) have rarely been used in this population.2

Diabetes and cardiovascular disease: from evidence to clinical practice – position statement 2014 of Brazilian Diabetes Society

There is a very well known correlation between diabetes and cardiovascular disease but many health care professionals are just concerned with glycemic control, ignoring the paramount importance of controlling other risk factors involved in the pathogenesis of serious cardiovascular diseases. This Position Statement from the Brazilian Diabetes Society was developed to promote increased awareness in relation to six crucial topics dealing with diabetes and cardiovascular disease: Glicemic Control, Cardiovascular Risk Stratification and Screening Coronary Artery Disease, Treatment of Dyslipidemia, Hypertension, Antiplatelet Therapy and Myocardial Revascularization. The issue of what would be the best algorithm for the use of statins in diabetic patients received a special attention and a new Brazilian algorithm was developed by our editorial committee. This document contains 38 recommendations which were classified by their levels of evidence (A, B, C and D). The Editorial Committee included 22 specialists with recognized expertise in diabetes and cardiology.

Influence of leukocytes and glycemia on the prognosis of patients with acute myocardial infarction

BACKGROUND Previous studies have demonstrated that leukocytosis and hyperglycemia verified at the admission of patients with acute myocardial infarction (AMI) are associated with intrahospital mortality. However, little is known on the long-term impact of these markers. OBJECTIVE To evaluate the short-and long-term influence of the levels of glucose and leukocytes on the prognosis of patients with AMI. METHODS A total of 809 patients with AMI were retrospectively assessed (mean age: 63.2 +/- 12.87 yrs) and prospectively and consecutively included in a specific database. RESULTS a) At the intrahospital phase, the mean values were compared between patients that died and those who survived: Leukocytosis: 12156+/-5977 vs 10337+/-3528 (p=0.004, 95%CI = 976-2663); Glucose 176+/-105 mg/dl vs 140+/-72 mg/dl (p<0.001, 95%CI = 19.4 - 52.6), respectively. b) With the adjusted mode, the same pattern was observed [p values: 0.002 (t-ratio 3.05), 0.04 (t-ratio 2.06), respectively]. c) Long-term follow-up: the univariate analysis showed P values of 0.001 (t-ratio 3.3), <0.001 (t-ratio 4.16), respectively. The multivariate analysis showed P=0.001 (t-ratio 3.35), 0.08 (t-ratio 1.75), respectively. (d) After the exclusion of the intrahospital deaths, the leukocyte (P=0.989) and glucose levels (P=0.144) did not remain significantly correlated with mortality. The same result was observed at the multivariate analysis. CONCLUSION The levels of glucose and leukocytes at the hospital admission of patients with AMI are excellent predictors of intrahospital mortality and poor predictors of long-term death.Resumen Fundamento: Estudios previos demostraron que tanto la leucocitosis como la hiperglucemia verificadas cuando de la admision de pacientes con infarto agudo de miocardio (IAM), estan correlacionadas con la mortalidad intrahospitalaria. Sin embargo, poco se sabe acerca del impacto de esos marcadores a largo plazo. Objetivo: Evaluar, a corto y largo plazos, la influencia de los niveles de glucosa y leucocitos en el pronostico de pacientes con IAM.Metodos: Se analizaron, retrospectivamente, a 809 pacientes (edad promedio 63,2 ± 12,87 anos) con IAM, incluidos de forma prospectiva y consecutiva en banco de datos especifico.Resultados: a) En la fase intrahospitalaria se compararon los valores promedio obtenidos entre pacientes que murieron o supervivieron: leucocitosis 12.156±5.977 vs 10.337±3.528 (p=0.004, 95% IC= 976-2663); glucosa 176±105 mg/dl vs 140±72 mg/dl (p<0.001, 95% IC= 19.4 – 52.6), respectivamente. b) En el modo ajustado, se verifico el mismo es - tandar [valores de p: 0.002 (t-ratio 3.05), 0.04 (t-ratio 2.06), respectivamente]. c) Seguimiento a largo plazo: el analisis univariado revelo valores de P de 0.001 (t-ratio 3.3), <0.001 (t-ratio 4.16), respectivamente. Ya el analisis multivariado: P=0.001 (t-ratio 3,35), 0.08 (t-ratio 1,75), respectivamente. d) Tras la exclusion de las muertes intrahospitalarias, los niveles leucocitarios (P=0.989) y la glucemia (P=0.144) no permanecieron correlacionadas significativamente con la

Dengue: cardiac manifestations and implications in antithrombotic treatment

A dengue tem ampla distribuicao em areas tropicais, ocorrendo de forma endemica e eventualmente epidemica. E transmitida por mosquitos do genero Aedes, principalmente Aedes aegypti, cuja distribuicao e adaptacao em ambientes urbanos e peridomiciliares explica a predominância da dengue em cidades. A doenca ocorre com a introducao de paciente viremico em ambiente onde ha concentracao suficiente de vetores, e torna-se epidemica com grandes aumentos na concentracao desses. O virus subdivide-se em quatro sorotipos, que nao conferem imunidade cruzada.

Increasing Doses of Simvastatin Versus Combined Ezetimibe/Simvastatin Effect on Circulating Endothelial Progenitor Cells

Background: Patients with coronary artery disease (CAD) should be treated with statins to attain very low cholesterol levels, in order to reduce cardiovascular adverse events. More than 70% of these patients do not reach the appropriate cholesterol goal despite moderate statin doses. However, it is not known whether therapeutic uptitration with different lipid-lowering strategies has a similar “pleiotropic” effect on atherosclerotic endothelial dysfunction evaluated by measurement of endothelial progenitor cells (EPCs). Objective: We sought to compare, in patients with stable CAD and with a low-density lipoprotein cholesterol (LDL-C) >70 mg/dL on treatment with simvastatin 20 mg, the effects on EPCs by increasing simvastatin to 80 mg versus adding ezetimibe 10 mg. Methods: Patients (n = 68, 63 ± 9 years, 39% men) were randomly allocated to receive ezetimibe 10/simvastatin 20 mg or simvastatin 80 mg for 6 weeks. Circulating EPCs were measured by flow cytometry before and after the treatment. Results: Both strategies presented similar effects on metabolic parameters. The LDLs were equally reduced by ezetimibe 10/simvastatin 20 mg and simvastatin 80 mg (28.9% ± 13% vs 21.1% ± 33%; P = .46, respectively). The levels of EPCs were unaffected by ezetimibe 10/simvastatin 20 mg (median [25th, 75th]: pre- vs posttreatment, 7.0 [2.3; 13.3] vs 3.1 [0.1; 13.2] EPCs/104 mononuclear cells; P = .43) or simvastatin 80 mg (pre- vs posttreatment, 6.1 [2.9; 15.2] vs 4.0 [1.4; 10.7] EPCs/104 mononuclear cells; P = .5) ,and there were no differences between the groups on treatment effects (P = .9). Conclusions: Among stable patients with CAD and with an LDL-C >70 mg/dL on simvastatin 20 mg, increasing simvastatin dose to 80 mg or adding ezetimibe 10 mg promoted similar further cholesterol reduction but did not have incremental effects on circulating EPCs. These data suggest that the effects of simvastatin moderate doses on EPCs are not increased by intensive lipid-lowering strategies (clinicaltrials.gov: NCT00474123).

P2Y12 receptor inhibition with prasugrel and ticagrelor in STEMI patients after fibrinolytic therapy: Analysis from the SAMPA randomized trial☆

BACKGROUND A pharmacodynamic comparison between ticagrelor and prasugrel after fibrinolytic therapy has not yet been performed. METHODS In the single-center SAMPA trial, 50 consecutive STEMI patients previously treated with clopidogrel and undergoing a pharmacoinvasive strategy were randomized to either a ticagrelor (n=25) 180mg loading dose followed by 90mg bid, or a prasugrel (n=25) 60mg loading dose followed by 10mg/day, initiated after fibrinolytic therapy but before angiography. Platelet reactivity was assessed with the VerifyNow P2Y12 assay at 0, 2, 6, and 24h after randomization. RESULTS Mean times from fibrinolysis to prasugrel or ticagrelor administration were 11.1±6.9 and 13.3±6.3h, respectively (p=0.24). The values of PRU decreased significantly from baseline to 2h (all p<0.001) and from 2h to 6h (all p<0.001) in both groups. There was no difference in PRU values between 6h and 24h. The mean PRU values at 0, 2, 6, and 24h were 234.9, 127.8, 45.4, and 48.0 in the prasugrel group and 233.1, 135.1, 67.7, and 56.9 in the ticagrelor group, respectively. PRU values did not significantly differ between groups at any time period of the study. CONCLUSIONS In patients with STEMI treated with fibrinolytic therapy, platelet inhibition after clopidogrel is suboptimal and can be further increased with more potent agents. Ticagrelor and prasugrel demonstrated a similar extent of P2Y12 receptor inhibition within 24h, although maximal platelet inhibition after these potent agents was not achieved for 6h.

Effect of β-blockers on the risk of atrial fibrillation in patients with acute myocardial infarction

INTRODUCTION: Oral β-blockers improve the prognosis of patients with acute myocardial infarction, while atrial fibrillation worsens the prognosis of this population. The reduction of atrial fibrillation incidence in patients treated with β-blockers could at least in part explain the benefits of this drug. OBJECTIVE: To investigate the effect of β-blockers on the incidence of atrial fibrillation in patients with acute myocardial infarction. METHODS: We analyzed 1401 patients with acute myocardial infarction and evaluated the occurrence or absence of atrial fibrillation, the use of oral β-blockers and mortality during the first 24 hours. RESULTS: a) The use of β-blockers was inversely correlated with the presence of atrial fibrillation (ρ = 0.004; OR = 0.54). b) Correlations with mortality were as follows: 31.5% in patients with atrial fibrillation, 9.2% in those without atrial fibrillation (ρ < 0.001; Odds Ratio = 4.52), and 17.5% in patients not treated with β-blockers and 6.7% in those who received the drug (ρ < 0.001; OR = 0.34). c) Adjusted Models: The presence of atrial fibrillation was independently correlated with mortality (OR = 2.48, ρ = 0.002). The use of β-blockers was inversely and independently correlated with mortality (OR = 0.53; ρ = 0.002). The patients who used β-blockers showed a lower risk of atrial fibrillation (OR = 0.59; ρ = 0.029) in the adjusted model. CONCLUSION: The presence of atrial fibrillation and the absence of oral β-blockers increased in-hospital mortality in patients with acute myocardial infarction. Oral β-blockers reduced the incidence of atrial fibrillation, which might be at least partially responsible for the drug’s benefit.