0000000000104210

AUTHOR

Michel Farnier

ROUTINE APPLICATION OF A LIPID-LOWERING TREATMENT ALGORITHM BEFORE DISCHARGE AFTER ACUTE MYOCARDIAL INFARCTION DESIGNED TO TARGET AN LDL-C < 55 MG/DL (1.4 MMOL/L)

research product

Mass Concentration of Plasma Phospholipid Transfer Protein in Normolipidemic, Type IIa Hyperlipidemic, Type IIb Hyperlipidemic, and Non–Insulin-Dependent Diabetic Subjects as Measured by a Specific ELISA

Abstract —Mean plasma phospholipid transfer protein (PLTP) concentrations were measured for the first time by using a competitive enzyme-linked immunosorbent assay. PLTP mass levels and phospholipid transfer activity values, which were significantly correlated among normolipidemic plasma samples ( r =0.787, P &lt;0.0001), did not differ between normolipidemic subjects (3.95±1.04 mg/L and 575±81 nmol · mL −1 · h −1 , respectively; n=30), type IIa hyperlipidemic patients (4.06±0.84 mg/L and 571±43 nmol · mL −1 · h −1 , respectively; n=36), and type IIb hyperlipidemic patients (3.90±0.79 mg/L and 575±48 nmol · mL −1 · h −1 , respectively; n=33). No significant correlations with plasma lipid p…

research product

Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia.

Hypercholesterolemic patients (n = 1,547) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol (LDL-C) levels ≥100 and ≤160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter, randomized, double-blind, active-controlled, clinical trial using two 6-week study periods. Period I compared the efficacy/safety of (1) adding ezetimibe 10 mg (ezetimibe) to stable atorvastatin 10 mg, (2) doubling atorvastatin to 20 mg, or (3) switching to rosuvastatin 10 mg. Subjects in the latter 2 groups who persisted with elevated LDL-C levels (≥100 and ≤160 mg/dl) after period I, entered period II; subjects on atorvastatin 20 mg had ezetimibe added to th…

research product

Prevalence and impact of metabolic syndrome on hospital outcomes in acute myocardial infarction.

The impact of metabolic syndrome after acute myocardial infarction (AMI) has not yet been studied. In a population-based sample of patients with AMI, we sought to determine the prevalence of metabolic syndrome in patients with AMI, its impact on hospital outcomes, and to assess the relative influence of each of the components of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III definition of metabolic syndrome on the risk of death and heart failure.A total of 633 unselected, consecutive patients hospitalized with AMI were categorized according to the NCEP ATP III metabolic syndrome criteria (presence of/=3 of the following: hyperglycemia; triglyceride level/=…

research product

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome.

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with ( n=368) and without ( n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least squares mean percent change from baseline and 95% confidence intervals in lipid efficacy parameters were calculated for the population and within subgroups. Treatment with ezetimibe/simvastatin was significantly more effect…

research product

Analysis of vitamin D levels in patients with and without statin-associated myalgia — A systematic review and meta-analysis of 7 studies with 2420 patients

article i nfo Introduction: VitaminD (vitD)deficiencymay beassociatedwith anincreased riskof statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. Methods: The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantita- tive data synthesis was performed using a fixed-effect model. Results: The electronic search yielde…

research product

Prevalence, risk factor burden, and severity of coronary artery disease in patients with heterozygous familial hypercholesterolemia hospitalized for an acute myocardial infarction: Data from the French RICO survey

Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described, especially for French patients.The objective of this study was to assess the prevalence of FH and severity of CAD from a large database of a French regional registry of acute MI.All consecutive patients hospitalized for an acute MI in a multicenter database from 2001 to 2017 were considered. FH was diagnosed using an algorithm adapted from the Dutch Lipid Clinic Network criteria. The prevalence and clinical features of FH and the severity of CAD were assessed.Among the 11,624 patients included i…

research product

An innovative lipid-lowering approach to enhance attainment of low-density lipoprotein cholesterol goals

Aims To improve attainment of LDL-cholesterol (LDL-c) targets, an expert group proposed an algorithm for lipid-lowering therapy during hospitalization for acute coronary syndrome and during follow-up. We aimed to assess adherence to this algorithm, and evaluate its impact on LDL-c levels and on attainment of therapeutic LDL-c targets in a population of post-acute coronary syndrome patients. Methods and results Prospective, observational study including patients admitted for acute coronary syndrome between February 2017 and September 2018. Patients admitted without statins or ezetimibe were considered ‘naïve’. Baseline LDL-c was admission LDL-c in naïve patients, and for those taking lipid-…

research product

P4573In patients with acute myocardial infarction, PCSK9 levels do not predict severity and recurrence of cardiovascular events

Abstract Background In patients with coronary artery disease (CAD), it remains unclear whether serum PCSK9 levels can predict the severity of the disease and the risk of future cardiovascular events. Methods Among the patients admitted for an acute myocardial infarction (MI) from September 2015 to December 2016 in an intensive care unit from a university hospital, serum PCSK9 levels were measured on admission in patients not previously receiving statin therapy. We aimed to evaluate the association between PCSK9 levels, metabolic parameters, severity of CAD on coronary angiography, and the risk of in-hospital events and at one-year follow-up. Results In a total of 648 patients (mean age: 66 …

research product

Long-term outcomes after acute myocardial infarction in patients with familial hypercholesterolemia: The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction program.

Patients with familial hypercholesterolemia (FH) are prone to develop acute myocardial infarction (AMI) at a younger age.The aim of the present study was to assess 5-year outcomes after AMI according to the presence of FH in a large multicenter cohort of patients.The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction consists of nationwide surveys recruiting patients over a 1- to 2-month period every 5 years. Patients recruited in 2005 and 2010 were followed up to 5 years.Of 5147 patients discharged alive and in whom FH status could be assessed, 2.8% had probable/definite FH, using an adapted Dutch Lipid Clinic score. They were 12 years younger, on average, tha…

research product

Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial

OBJECTIVE: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053).METHODS: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoi…

research product

Treatment effect of alirocumab according to age group, smoking status, and hypertension: Pooled analysis from 10 randomized ODYSSEY studies

Background: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. Objective: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. Methods: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24–104 weeks’ duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non–familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75…

research product

Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study

SUMMARY Aims: To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe ⁄simvastatin (EZE ⁄SIMVA) 10 ⁄20 mg vs. rosuvastatin (ROSUVA) 10 mg. Methods: In this randomised, double-blind study, 618 patients with documented hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) ‡ 2.59 and £ 4.92 mmol ⁄l] and with high cardiovascular risk who were taking a stable daily dose of one of several statin medications for ‡ 6 weeks prior to the study randomisation visit entered a 6-week open-label stabilisation ⁄screening period during which they continued to receive their prestudy statin dose. Following stratification by study site and statin dose ⁄potency, patien…

research product

Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force

International audience; Background and aimsThis European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients.MethodsEvidence-based review.ResultsStatin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-h…

research product

Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Dat…

research product

Circulating leukocyte telomere length and oxidative stress: A new target for statin therapy

International audience; Objectives: We investigated the relationship between prior statin therapy and leukocyte telomere length (LTL), as well as their interaction with potential new biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen species-induced inflammation.Methods and results: From patients admitted for an acute myocardial infarction, LTL was assessed by quantitative polymerase chain reaction (Q-PCR), and leukocyte Finkel-Biskis-Jinkins osteosarcoma (FOS) and 8-oxoguanine DNA glycosylase (OGG1) messenger ribonucleic acid (mRNA) levels were measured by retrotranscription Q-PCR. Patients under prior chronic statin therapy were compared with patients without …

research product

P233 Efficacité comparative de ézétimibe/simvastatine 10/20 mg et de rosuvastatine 10 mg chez des patients à haut risque en fonction de la présence ou non d’un diabète de type 2 et/ou d’un syndrome métabolique

Introduction L'objectif de cette analyse pos-hoc a ete de comparer l'efficacite de deux traitements (ezetimibe/simvastatine 10/20 mg et rosuvastatine 10 mg) chez des patients a haut risque cardiovasculaire non a l'objectif LDL-cholesterol (LDL-C) sous statine avec ou sans diabete de type 2 (DT2) d'une part et avec ou sans syndrome metabolique (definition NCEP ATP III) d'autre part. Patients et Methodes 618 patients a haut risque avec LDL-C ≥ 1,0 g/l et ≤ 1,6 g/l malgre un traitement par statine ont ete randomises en double-aveugle et traites pendant 6 semaines soit par ezetimibe/simvastatine 10/20 mg, soit par rosuvastatine 10 mg. L'efficacite des deux traitements a ete comparee chez les pa…

research product

Switching from statin monotherapy to ezetimibe/simvastatin or rosuvastatin modifies the relationships between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients at high risk of coronary disease

OBJECTIVE: To evaluate relationships between apolipoprotein B (Apo B), LDL cholesterol (LDL-C), and non-HDL-C in high-risk patients treated with lipid-lowering therapy. DESIGN AND METHODS: This post-hoc analysis calculated LDL-C and non-HDL-C levels corresponding to an Apo B of 0.9 g/L following treatment with 1) statin monotherapy (baseline) and 2) ezetimibe/simvastatin 10/20mg or rosuvastatin 10mg (study end). The percentages of patients reaching LDL-C, non-HDL-C, and Apo B targets were calculated at study end. RESULTS: After switching to ezetimibe/simvastatin or rosuvastatin, the LDL-C and non-HDL-C corresponding to Apo B=0.9 g/L were closer to the more aggressive LDL-C and non-HDL-C goa…

research product

2214Prevalence and severity of coronary disease in patients with familial hypercholesterolemia hospitalized for an acute myocardial infarction: data from the RICO survey

Abstract Aim Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described. From a large database of a regional registry of acute MI, we aimed to address prevalence of FH and severity of CAD. Methods Consecutive patients hospitalized with MI in a multicentre database from 2001–2017 were considered. An algorithm, adapted from Dutch Lipid Clinic Network criteria, was built upon 4 variables (LDL-cholesterol (LDL-C) and lipid lowering agents, premature and family history of CAD) to identify FH probabilities. Results Among the 11624 patients included in the surv…

research product

Abstract 18967: Analysis of Vitamin D Levels in Patients With and Without Statin-induced Myalgia - A Systematic Review and Meta-analysis of 7 Studies with 2416 Patients

Introduction: Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related muscle complaints, and symptomatic myalgia in statin-treated patients. Hypothesis: The aim of this meta-analysis was to investigate whether subjects with statin-induced myalgia have lower serum vit D levels compared with those who are asymptomatic. Methods: We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to March 2014) to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Results: The electronic search yielded 4…

research product

Lipid-lowering therapy and low-density lipoprotein cholesterol goal achievement in patients with acute coronary syndromes: The ACS patient pathway project

Background and aims: Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. Aim of this survey was to evaluate the compliance to ESC/EAS guidelines during the management of ACS patients and the effectiveness of secondary prevention in seven European countries.Methods: By means of an online questionnaire, data on 2775 ACS patients (either acute case or follow-up patients) were collected, including data on lipid profile, medications, follow-up visit planning, screening for familial hypercholesterolemia.Results: Lipid profiles were obtained for 91% of ACS patients in the acute phase…

research product

0132: Identifying familial hypercholesterolemia from registries of patients with acute myocardial infarction: an algorithm-based approach

Background and aims Familial hypercholesterolemia (FH) is at very high risk of early myocardial infarction (MI). The prevalence of FH, which is estimated to be at least 1:500 in the general population, remains unclear in patients with acute MI. From databases of 2 French regional and nationwide registries of acute MI (RICO and FAST-MI, respectively), we aimed to determine FH prevalence by developing a specific algorithm. Methods and results Consecutive patients with AMI ≤48 hours of onset included 1) in FAST-MI: during a one-month period in 213 institutions at the end of 2005 and 2) in RICO: from January 2001 December 2013 (≈13y), were considered in the 2 databases. The algorithm was adapte…

research product

0133 : Identifying familial hypercholesterolemia from registries of patients with acute myocardial infarction: an algorithm-based approach

Background and aim Familial hypercholesterolemia (FH) is at very high risk of early myocardial infarction (MI). The prevalence of FH, which is estimated to be at least 1:500 in the general population, remains unclear in patients with acute MI. From databases of 3 French regional and nationwide registries of acute MI (RICO and FAST-MI 2005 and 2010, respectively), we aimed to determine FH prevalence by developing a specific algorithm. Methods and results Consecutive patients with AMI ≤48 hours of onset included 1) in FAST-MI : during a one-month period in 223 institutions at the end of 2005 and 213 institutions at the end of 2010, and 2) in RICO :from January 2001 – December 2013 (≈ 13 y), w…

research product

Ezetimibe/Simvastatin 10/20 mg versus Rosuvastatin 10 mg in high-risk hypercholesterolemic patients stratified by prior statin treatment potency

Abstract Objective This post-hoc analysis compared the lipid-altering efficacy of Ezetimibe/Simvastatin 10/20 mg (EZ/Simva) versus Rosuvastatin 10 mg (Rosuva) in patients stratified by statin potency/dose prior to randomization. Methods Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite prior statin treatment (n = 618) were randomized 1:1 to EZ/Simva 10/20 mg or Rosuva 10 mg for 6 weeks. Percent change from baseline in lipids and attainment of lipid targets were assessed within each subgroup (low potency n = 369, high potency n = 249). Consistency of the treatment effect across subgroups was evaluated by testing for treatment-by-subgroup interaction. No multiplicity …

research product

Lipid-Altering Efficacy of Ezetimibe/Simvastatin 10/20 mg Compared to Rosuvastatin 10 mg in High-Risk Patients with and without Type 2 Diabetes Mellitus Inadequately Controlled Despite Prior Statin Monotherapy

SUMMARY Aims: This post hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) or rosuvastatin 10 mg (ROSUVA) in uncontrolled high-risk hypercholesterolemic patients with/without type 2 diabetes mellitus (T2DM) despite statin monotherapy. Methods: Patients (n = 618) at high risk for coronary vascular disease with elevated LDL-C ≥100 and ≤190 mg/dL despite use of statins were randomized 1:1 to double-blind EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patients were classified as having T2DM based on ≥1 of the following: diagnosis of T2DM, antidiabetic medication, or FPG ≥126 mg/dL. This analysis evaluated percent changes from baseline in lipids among p…

research product

High Serum Cholesteryl Ester Transfer Rates and Small High-Density Lipoproteins Are Associated With Young Age in Patients With Acute Myocardial Infarction

Objectives Our aim was to characterize cholesteryl ester transfer protein (CETP) activity in the early phase of acute myocardial infarction (MI). Background Cholesteryl ester transfer protein catalyzes the transfer of cholesteryl esters from high-density lipoprotein (HDL) donors to apolipoprotein B-containing lipoprotein acceptors. Methods The CETP concentration, lipid profiles, and the rate of cholesteryl ester transfer (CET) from a tracer dose of radiolabeled HDL toward endogenous lipoproteins were determined within 24 h after symptom onset. Results Among 347 patients with first MI, CETP concentration, triglycerides, and non–HDL-cholesterol increased across tertiles of the CET rate, where…

research product

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin-associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10 – 15% of patients.In clinical practice, statin intolerance limits effectiv…

research product

Position paper Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10-15% of patients. In clinical practice, statin intolerance limits effective…

research product