0000000000206982
AUTHOR
Dragos Vinereanu
Early Treatment With Zofenopril and Ramipril in Combination With Acetyl Salicylic Acid in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: Results of a 5-Year Follow-up of Patients of the SMILE-4 Study
Abstract: The SMILE-4 study showed that in patients with left ventricular dysfunction (LVD) after acute myocardial infarction, early treatment with zofenopril plus acetyl salicylic acid is associated with an improved 1-year survival, free from death or hospitalization for cardiovascular (CV) causes, as compared to ramipril plus acetyl salicylic acid. We now report CV outcomes during a 5-year follow-up of the patients of the SMILE-4 study. Three hundred eighty-six of the 518 patients completing the study (51.2%) could be tracked after the study end and 265 could be included in the analysis. During the 5.5 (±2.1) years of follow-up, the primary endpoint occurred in 27.8% of patients originall…
Echocardiographic reference ranges for normal left ventricular 2D strain: results from the EACVI NORRE study
International audience; Aims - To obtain the normal ranges for 2D echocardiographic (2DE) measurements of left ventricular (LV) strain from a large group of healthy volunteers accounting for age and gender. Methods and results - A total of 549 (mean age: 45.6 ± 13.3 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. 2DE data sets have been analysed with a vendor-independent software package allowing homogeneous measurements irrespective of the echocardiographic equipment used to acquire the data sets. The lowest expected values of LV strains and twist calculated as ± 1.96 standard deviations from the mean…
Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure
Background— Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results— We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of med…
Normal Reference Ranges for Echocardiography: Rationale, study design, and methodology (NORRE Study)
International audience; BACKGROUND: Availability of normative reference values for cardiac chamber dimensions, volumes, mass, and function is a prerequisite for the accurate application of echocardiography for both clinical and research purposes. However, due to the lack of consistency in current echocardiographic 'reference values', their use for clinical decision-making remains questionable. AIMS: The aim of the 'Normal Reference Ranges for Echocardiography Study (NORRE Study)' is to obtain a set of 'normal values' for cardiac chamber geometry and function in a large cohort of healthy Caucasian individuals aged over a wide range of ages (25-75 years) using both conventional and advanced e…
Echocardiographic reference ranges for normal cardiac Doppler data: results from the NORRE Study
International audience; AIMS: Reference values for Doppler parameters according to age and gender are recommended for the assessment of heart physiology, specifically for left ventricular (LV) diastolic function. In this study, we report normal reference ranges for Doppler parameters obtained in a large group of healthy volunteers. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following Doppler acquisition and measurement protocols approved by the European Association of Cardiovascular Imaging. METHODS AND RESULTS: A total of 449 (mean age: 45.8 ± 13.7 years) healthy volunteers (198 men and 251 women) were enrolled at the collaborating institutions…
Zofenopril and Ramipril in Combination with Acetyl Salicylic Acid in Postmyocardial Infarction Patients with Left Ventricular Systolic Dysfunction: A Retrospective Analysis of the SMILE-4 Randomized, Double-Blind Study in Diabetic Patients
Summary Objective In the SMILE-4 study, zofenopril + acetyl salicylic acid (ASA) was more effective than ramipril + ASA on 1-year prevention of major cardiovascular events (MACE) in patients with acute myocardial infarction complicated by left ventricular dysfunction. In this retrospective analysis, we evaluated drug efficacy in subgroups of patients, according to a history of diabetes mellitus. Methods The primary study endpoint was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Diabetes was defined according to medical history (previous known diagnosis). Results A total of 562 of 693 (81.0%) patients were classified as nondiabetics and 131 (18.9%) as dia…
Impact of nutraceuticals on markers of systemic inflammation: Potential relevance to cardiovascular diseases - A position paper from the International Lipid Expert Panel (ILEP).
Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not en…
Echocardiographic reference ranges for normal cardiac chamber size: Results from the NORRE study
AimsAvailability of normative reference values for cardiac chamber quantitation is a prerequisite for accurate clinical application of echocardiography. In this study, we report normal reference ranges for cardiac chambers size obtained in a large group of healthy volunteers accounting for gender and age. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following chamber quantitation protocols approved by the European Association of Cardiovascular Imaging.MethodsA total of 734 (mean age: 45.8 ± 13.3 years) healthy volunteers (320 men and 414 women) were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORR…
Zofenopril and ramipril in patients with left ventricular systolic dysfunction after acute myocardial infarction: A propensity analysis of the Survival of Myocardial Infarction Long-term Evaluation (SMILE) 4 study
Introduction: This was a propensity score analysis of the prospective, randomized, double-blind Survival of Myocardial Infarction Long-term Evaluation (SMILE) 4 study in which one-year treatment with zofenopril 60 mg plus acetylsalicylic acid (ASA) 100 mg gave superior results compared to ramipril 10 mg plus ASA in terms of death or hospitalization for cardiovascular causes in patients with acute myocardial infarction (AMI) complicated by left ventricular dysfunction (LVD). Materials and methods: A total of 716 patients of the intention-to-treat population were divided into homogeneous propensity quintiles (Q) using a logistic regression model (QI: best risk profile; QV: worst risk profile)…
Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4.
Claudio Borghi,1 Ettore Ambrosioni,1 Stefano Omboni,2 Arrigo FG Cicero,1 Stefano Bacchelli,1 Daniela Degli Esposti,1 Salvatore Novo,3 Dragos Vinereanu,4 Giuseppe Ambrosio,5 Giorgio Reggiardo,6 Dario Zava7 1Unit of Internal Medicine, Policlinico S Orsola, University of Bologna, Bologna, Italy; 2Italian Institute of Telemedicine, Varese, Italy; 3Division of Cardiology, University of Palermo, Palermo, Italy; 4University and Emergency Hospital, Bucharest, Romania; 5Division of Cardiology, University of Perugia, Perugia, Italy; 6Mediservice, Milano, Italy; 7Istituto Lusofarmaco d'Italia SpA, Peschiera Borromeo, Italy Background: In SMILE-4 (the Survival of Myocardial Infarction Long-term…
A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure
Aims: Although active-controlled trials with renin–angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos.\ud \ud Methods and results: We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidit…
Cost effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post- hoc analysis of the smile-4 study
BACKGROUND: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. METHODS: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study end…
Echocardiographic reference ranges for normal left ventricular layer-specific strain: results from the EACVI NORRE study
Abstract Aims To obtain the normal range for 2D echocardiographic (2DE) measurements of left ventricular (LV) layer-specific strain from a large group of healthy volunteers of both genders over a wide range of ages. Methods and results A total of 287 (109 men, mean age: 46 ± 14 years) healthy subjects were enrolled at 22 collaborating institutions of the EACVI Normal Reference Ranges for Echocardiography (NORRE) study. Layer-specific strain was analysed from the apical two-, three-, and four-chamber views using 2DE software. The lowest values of layer-specific strain calculated as ±1.96 standard deviations from the mean were −15.0% in men and −15.6% in women for epicardial strain, −16.8% …
Randomised comparison of zofenopril and ramipril plus acetylsalicylic acid in postmyocardial infarction patients with left ventricular systolic dysfunction: a post hoc analysis of the SMILE-4 Study in patients according to levels of left ventricular ejection fraction at entry
Objective Conflicting evidence exists on the benefits of treating patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF) with an ACE inhibitor. This retrospective analysis of the SMILE-4 Study sought to compare the efficacy of zofenopril 60 mg plus acetylsalicylic acid (ASA) versus ramipril 10 mg plus ASA 100 mg in patients with acute myocardial infarction (AMI) and heart failure, according to an impaired or preserved LVEF. Methods The primary study end point was 1-year combined occurrence of death or hospitalisation for cardiovascular causes. A preserved LVEF was defined by a baseline LVEF >40% and an impaired one by an LVEF ≤40%. Results 448 patients…
Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo
BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated.METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population …
Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.
1.1. Cardiovascular disease and dyslipidemia: prevalence and global economic impact Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, reaching 31% of deaths in 2012 [1]. In particular, atherosclerosis and ischemic heart disease (IHD) are the main causes of premature death in Europe and are responsible for 42% of deaths in women and 38% in men under 75 years old [2]. The global economic impact of CVD is estimated to have been US $906 billion in 2015 and is expected to rise by 22% by 2030 [3]. Cardiovascular diseases also represent the major cause of disability in developed countries. It has been estimated that their growing burden could lead to a global increase in…
3D echocardiographic reference ranges for normal left ventricular volumes and strain: results from the EACVI NORRE study
International audience; Aim: To obtain the normal ranges for 3D echocardiography (3DE) measurement of left ventricular (LV) volumes, function, and strain from a large group of healthy volunteers. Methods and results: A total of 440 (mean age: 45 ± 13 years) out of the 734 healthy subjects enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study had good-quality 3DE data sets that have been analysed with a vendor-independent software package allowing homogeneous measurements regardless of the echocardiographic machine used to acquire the data sets. Upper limits of LV end-diastolic and end-systolic volumes were larger in men (97 and 42 mL/m2)…
Two-dimensional transthoracic echocardiographic normal reference ranges for proximal aorta dimensions: Results from the EACVI NORRE study
International audience; AIMS: To report normal reference ranges for echocardiographic dimensions of the proximal aorta obtained in a large group of healthy volunteers recruited using state-of-the-art cardiac ultrasound equipment, considering different measurement conventions, and taking into account gender, age, and body size of individuals. METHODS AND RESULTS: A total of 704 (mean age: 46.0 ± 13.5 years) healthy volunteers (310 men and 394 women) were prospectively recruited from the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained in all subjects following pre-defined protocols. Aortic…
Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP)
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the dis…
Echocardiographic reference ranges for normal non-invasive myocardial work indices: results from the EACVI NORRE study
International audience; Aims - To obtain the normal ranges for 2D echocardiographic (2DE) indices of myocardial work (MW) from a large group of healthy volunteers over a wide range of ages and gender. Methods and results - A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from left ventricle (LV) pressure-strain loops. Peak LV systolic pressure was non-invasively derived from brachial artery cuff pressure. The lowest values of MW indic…
Statin therapy in athletes and patients performing regular intense exercise - Position paper from the International Lipid Expert Panel (ILEP)
Abstract Acute and chronic physical exercises may enhance the development of statin-related myopathy. In this context, the recent (2019) guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend that, although individuals with dyslipidemia should be advised to engage in regular moderate physical exercise (for at least 30 min daily), physicians should be alerted with regard to myopathy and creatine kinase (CK) elevation in statin-treated sport athletes. However it is worth emphasizing that abovementioned guidelines, previous and recent ESC/EAS consensus papers on adverse effects of statin therapy as wel…
Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study
Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing…
Correlation between non-invasive myocardial work indices and main parameters of systolic and diastolic function
Abstract Aims The present study sought to evaluate the correlation between indices of non-invasive myocardial work (MW) and left ventricle (LV) size, traditional and advanced parameters of LV systolic and diastolic function by 2D echocardiography (2DE). Methods and results A total of 226 (85 men, mean age: 45 ± 13 years) healthy subjects were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. Global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE) were estimated from LV pressure-strain loops using custom software. Peak LV pressure was estimated non-invasively from brachial ar…
Zofenopril is a cost-effective treatment for patients with left ventricular systolic dysfunction following acute myocardial infarction: a pharmacoeconomic analysis of the SMILE-4 study
Objective: The Survival of Myocardial Infarction Long-term Evaluation 4 Study (SMILE-4) showed the superiority of Zofenopril (Z) associated with Acetylsalicylic Acid (ASA) as respect to Ramipril (R) plus ASA in reducing the occurrence of major cardiovascular events, in patients with left ventricular dysfunction (LVD) following Acute Myocardial Infarction (AMI). The objective of this retrospective analysis was the evaluation of cost-effectiveness of Z compared to R. Methods: 771 patients with LVD and AMI were randomized, double-blind to Z 60 mg/day (n=389) or R 10 mg/day (n=382) plus ASA 100 mg/day and followed-up for 1 year. The primary study end-point was 1-year combined occurrence of deat…
Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel
In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is…
The Role of Nutraceuticals in Statin Intolerant Patients.
Abstract Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activ…