PubMed Health⌕ Search

Biomedical subjects

Michel Farnier

Publications and source records attributed to Michel Farnier.

11 recordsLinked to original sources
PubMed2006

Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia.

OBJECTIVES: This study sought to determine the long-term safety and efficacy of co-administered fenofibrate (FENO) and ezetimibe (EZE) in patients with mixed hyperlipidemia. BACKGROUND: Both EZE and FENO offer complementary benefits to the lipid profile of patients with mixed hyperlipidemia. METHODS: After completing the 12-week randomized, double-blind base study that compared EZE 10 mg, FENO 160 mg, FENO 160 mg plus EZE 10 mg, and placebo in patients with mixed hyperlipidemia, patients continued into a double-blind, 48-week extension phase. Those patients in the FENO plus EZE and FENO groups continued on their respective base study treatment, and patients in the EZE and placebo groups were switched to FENO plus EZE and FENO, respectively. RESULTS: Of the 587 patients who completed the base study, 576 continued into the extension study (n = 340 in FENO plus EZE and n = 236 in FENO). The FENO plus EZE produced significantly greater reductions in low-density lipoprotein-cholesterol compared with FENO (-22% vs. -9%, respectively; p < 0.001). There were also significantly greater improvements in triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol, non-HDL-C, and apolipoprotein B with FENO plus EZE compared with FENO. Changes in apolipoprotein A-I and high-sensitivity C-reactive protein were similar between groups. Overall, FENO plus EZE was well tolerated during the extension study. The proportion of patients with consecutive elevations of alanine aminotransferase/aspartate aminotransferase > or =3 times upper limit of normal were similar between the FENO plus EZE (1.2%) and FENO (1.7%) groups. No cases of creatine phosphokinase elevations > or =10 times upper limit of normal or myopathy were observed in either group. CONCLUSIONS: Long-term, 48-week co-administration of FENO plus EZE was well tolerated and more efficacious than FENO in patients with mixed hyperlipidemia.

Adult↗
PubMed2005

Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease.

OBJECTIVE: To determine whether co-administering ezetimibe with on-going simvastatin treatment was more effective than placebo plus on-going simvastatin in achieving an LDL-C treatment target of < or = 2.60 mmol/l (100 mg/dl) in hypercholesterolemic patients with coronary heart disease (CHD). METHODS: Men and women (age > or = 18 years) with documented CHD and on a stable dose of simvastatin 10 mg or 20 mg for at least 6 weeks were recruited for this study. After a 4-week simvastatin 10 or 20 mg plus placebo and diet run-in period, patients were eligible for randomization if LDL-C > 2.60 and < or = 4.20 mmol/l and triglycerides (TG) < or = 4.00 mmol/l. Eligible patients were randomized to a double-blind comparative study with ezetimibe 10 mg co-administered with on-going simvastatin 10 mg or 20 mg (n=181) versus placebo to match ezetimibe co-administered with simvastatin 10 mg or 20 mg (n=191) for 6 weeks. RESULTS: At baseline, mean LDL-C was comparable between the ezetimibe (3.14 mmol/l) and placebo (3.19 mmol/l) groups. With the addition of ezetimibe or placebo to on-going simvastatin therapy, the percentage of patients achieving the LDL-C goal of < or = 2.60 mmol/l after 6 weeks of treatment was significantly (p < or = 0.001) greater in the ezetimibe group (74.3%) than in the placebo group (16.7%). The addition of ezetimibe to on-going simvastatin treatment also resulted in a significantly (p < or = 0.001) larger mean percent reduction in LDL-C from baseline (25.2%) compared with placebo (0.9%). Ezetimibe was generally well tolerated compared to placebo when added to on-going simvastatin treatment. CONCLUSIONS: Co-administering ezetimibe with on-going simvastatin 10 or 20 mg treatment allowed more hypercholesterolemic patients with CHD to reach the LDL-C treatment target of < or = 2.60 mmol/l.

Anticholesteremic Agents↗
PubMed2005

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

BACKGROUND: 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. METHODS: 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 >/=150 mg/dL [>/=1.7 mmol/L]; high-density lipoprotein cholesterol level <40 mg/dL [<1.04 mmol/L] in men and <50 mg/dL [<1.30 mmol/L] in women; blood pressure >/=130/85 mm Hg; and waist circumference >102 cm in men or 88 cm in women). RESULTS: Among the 633 patients, 290 (46%) fulfilled the criteria for metabolic syndrome. Patients with metabolic syndrome were older and more likely to be women. Acute myocardial infarction characteristics and left ventricular ejection fraction rates were similar for both groups. In-hospital case fatality was higher in patients with metabolic syndrome compared with those without, as was the incidence of severe heart failure (Killip class >II). In multivariate analysis, metabolic syndrome was a strong and independent predictor of severe heart failure, but not in-hospital death. Analysis of the predictive value of each of the 5 metabolic syndrome components for severe heart failure showed that hyperglycemia was the major determinant (odds ratio, 3.31; 95% confidence interval, 1.86-5.87). CONCLUSIONS: In an unselected population of patients with AMI, the prevalence of metabolic syndrome was high. Metabolic syndrome appeared associated with worse in-hospital outcome, with a higher risk of development of severe heart failure. Among metabolic syndrome components, hyperglycemia was the main correlate of the risk of development of severe heart failure during AMI.

Aged↗
PubMed2005

Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia.

AIMS: To examine the efficacy and safety of coadministered ezetimibe (EZE) with fenofibrate (FENO) in patients with mixed hyperlipidaemia. METHODS AND RESULTS: This was a multicentre, randomized, double-blind, placebo-controlled, parallel arm trial in patients with mixed hyperlipidaemia [LDL-cholesterol (LDL-C), 3.4-5.7 mmol/L (2.6-4.7 mmol/L for patients with type 2 diabetes); triglycerides (TG), 2.3-5.7 mmol/L] and no history of coronary heart disease (CHD), CHD-equivalent disease (except for type 2 diabetes), or CHD risk score>20%. A total of 625 patients was randomized in a 1:3:3:3 ratio to one of four daily treatments for 12 weeks: placebo; EZE 10 mg; FENO 160 mg; FENO 160 mg plus EZE 10 mg (FENO+EZE). The primary endpoint compared the LDL-C lowering efficacy of FENO+EZE vs. FENO alone. LDL-C, non-HDL-cholesterol (non-HDL-C), and apolipoprotein B were significantly (P<0.001) reduced with FENO+EZE when compared with FENO or EZE alone. TG levels were significantly decreased and HDL-C was significantly increased with FENO+EZE and FENO treatments when compared with placebo (P<0.001). Coadministration therapy reduced LDL-C by 20.4%, non-HDL-C by 30.4%, TG by 44.0%, and increased HDL-C by 19.0%. At baseline, >70% of all patients exhibited the small, dense LDL pattern B profile. A greater proportion of patients on FENO+EZE and FENO alone treatments shifted from a more atherogenic LDL size pattern to a larger, more buoyant, and less atherogenic LDL size pattern at study endpoint than those on placebo or EZE. All three active therapies were well tolerated. CONCLUSION: Coadministration of EZE with FENO provided a complementary efficacy therapy that improves the atherogenic lipid profile of patients with mixed hyperlipidaemia.

Adolescent↗
PubMed2003

Effects of baseline level of triglycerides on changes in lipid levels from combined fluvastatin + fibrate (bezafibrate, fenofibrate, or gemfibrozil).

This analysis was conducted to evaluate the effect of baseline triglyceride levels on lipid and lipoprotein changes after treatment with the combination of fluvastatin and fibrates. The analysis involved pooling data from 10 studies that included 1,018 patients with either mixed hyperlipidemia or primary hypercholesterolemia. Patients received a combination of fluvastatin and a fibrate (bezafibrate, fenofibrate, or gemfibrozil) from 16 to 108 weeks. The combination of fluvastatin and a fibrate improved lipid profiles, with reductions in triglycerides, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol that were dependent on baseline triglyceride levels. The greatest triglyceride reductions were observed in patients with high baseline triglyceride levels (> or =400 mg/dl) (41%, p <0.0001). The greatest LDL cholesterol and non-HDL cholesterol reductions occurred in patients with normal baseline triglyceride levels (<150 mg/dl) (35% and 33%, respectively; p <0.0001). The combined fluvastatin-fibrate therapy was well tolerated. Two patients (0.2%) (1 patient on fluvastatin 80 mg + gemfibrozil 1,200 mg and 1 patient on fluvastatin 20 mg + fenofibrate 200 mg) had creatine kinase levels > or =10 times the upper limit of normal, 11 patients (1.1%) had an elevation in alanine transaminase >3 times the upper limit of normal, and 7 patients (0.7%) had elevations in aspartate transaminase >3 times the upper limit of normal. Combined fluvastatin-fibrate therapy takes advantage of the complementary effects of the 2 agents, with the extent of triglyceride, LDL cholesterol, and non-HDL cholesterol lowering dependent on baseline triglyceride levels. The combination of fluvastatin and fibrates was well tolerated with no major safety concerns.

Age Factors↗
PubMed2003

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.

Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.

Amino Acid Substitution↗
PubMed2003

Combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative: a critical review of potential benefits and drawbacks.

It has been clearly shown that lowering low density lipoprotein-cholesterol (LDL-C) [most often with an HMG-CoA reductase inhibitor] decreases the risk of a cardiovascular event. However, this risk reduction was, at most, 35% in clinical trials, meaning that many events could not be prevented. Moreover, reaching target lipid values as recommended by the current guidelines is often difficult, mainly in high-risk situations such as secondary prevention or type 2 diabetes mellitus. As the two main classes of lipid-lowering drugs (HMG-CoA reductase inhibitors and fibric acid derivatives) have complementary effects on lipid parameters, it seems logical to combine both treatments particularly in patients with combined hyperlipidemia. In fact, combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative induces a further decrease in LDL-C levels compared with monotherapy and improves other lipid values such as high density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) levels. Unfortunately, there are currently no available randomized, prospective clinical data on the reduction of the incidence of cardiovascular events with such a combination. This is mainly because the use of HMG-CoA reductase inhibitor and fibric acid derivative combinations was initially described as dangerous. It is true that such a combination increases the risk of muscle toxicity that already exists with monotherapy. Muscle toxicity can eventually lead to life-threatening rhabdomyolysis and some precautions of use are required; however, the risk seems actually lower than what has been initially reported. The use of combined therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative requires the respect of some rules such as avoiding the prescription in patients with concomitant conditions like renal failure and avoiding the use of gemfibrozil as a fibric acid derivative in such a combination. It is now imperative to design clinical trials to determine the clinical efficacy and precise safety of this combined treatment especially in patients with abnormalities in every parameter of the lipid triad (LDL, HDL and TG) and a high vascular risk such as patients with type 2 diabetes mellitus.

Cholesterol, HDL↗
PubMedDate not supplied

[New antilipemics: prospects].

The field of new lipid-lowering drug research is very active, with researchers, looking to make the currently available drugs more powerful and safer, and to develop new classes of drugs. Among the statins, development has gone the farthest for rosuvastatin and pitavastatin. Colesevelam is a new bile acid sequestrant with a better digestive tolerance. Among the new classes of drugs, the most promising molecules are the cholesterol absorption inhibitors--with ezetimibe as the first in line--and the PPAR-alpha and PPAR-gamma activators. Among the other classes, the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, and ileal bile acid transporter inhibitors, have to be mentioned. In most of the cases, those new compounds are being developed mainly as a combined treatment with statins. However, these combination therapies differ depending on the lipid abnormalities of the patient. The statin-ezitimibe and the statin-bile acid sequestrant combinations have been the most studied treatments in pure hypercholesterolaemia. On another hand, the statin-PPAR-alpha and -gamma activator combination were the first to be developed for patients with combined hyperlipidaemia or type 2 diabetes mellitus. However, the clinical benefit of ACAT or CETP inhibitors remains to be determined and the development of MTP inhibitors has been restricted so far, because of problems of digestive intolerance and hepatic steatosis. Finally, the discovery of new specific lipoprotein receptors, such as the ABCA1 and SRB1 receptors, means that we can work towards developing new potential targets for pharmacological intervention.

Animals↗