The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
Michel Farnier - One of the best experts on this subject based on the ideXlab platform.
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Combination Therapy with an HMG-CoA Reductase Inhibitor and a Fibric Acid Derivative
American Journal of Cardiovascular Drugs, 2003Co-Authors: Michel FarnierAbstract: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.
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combination therapy with an hmg coa reductase inhibitor and a Fibric Acid Derivative a critical review of potential benefits and drawbacks
American Journal of Cardiovascular Drugs, 2003Co-Authors: Michel FarnierAbstract: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.
Amelia E. Aránega - One of the best experts on this subject based on the ideXlab platform.
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Influence of Fibric Acid Derivatives on intermediate filament proteins in myocardiocyte cultures.
Life Sciences, 2002Co-Authors: F.j. Gonzalez, Celia Vélez, Amelia E. Aránega, M.a. Muros, Luis Alvarez, Ana Linares, Juan FernándezAbstract:Abstract We analyzed desmin and vimentin accumulation in chick myocardiocyte cultures treated with the Fibric Acid Derivatives bezafibrate, fenofibrate and gemfibrozil. The most noteworthy finding was the 50% decrease in the cytoplasmic desmin fraction in cells treated with gemfibrozil in comparison to control cultures, and the 19% increase in the cytoskeletal fraction in cultures treated with gemfibrozil and with bezafibrate. Vimentin accumulation by cells treated with bezafibrate was similar to that in control cultures, however the cytoskeletal vimentin fraction rose by 26% after treatment with gemfibrozil, and fell 13% after treatment with fenofibrate. No vimentin was found in the cytoplasmic fraction of cell treated with bezafibrate. Given the role of intermediate filaments in heart muscle contraction, Fibric Acid Derivative- induced changes in the cytoplasmic and cytoskeletal concentrations of intermediate filament proteins may be related with the secondary effects of these drugs on heart rate.
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Changes in subcellular accumulation of contractile proteins in myocardiocyte cultures: effects of Fibric Acid Derivatives.
Journal of Cardiovascular Pharmacology, 1993Co-Authors: Celia Vélez, Amelia E. Aránega, M.a. Muros, Consolación Melguizo, Amanda R. González, Luis AlvarezAbstract:: We analyzed the influence of 6 and 24 h of treatment with the Fibric Acid Derivatives bezafibrate (10 micrograms/ml), gemfibrozil (23 micrograms/ml), and fenofibrate (30 micrograms/ml) on alpha-actinin, troponin-T, and tropomyosin proteins in the cytoplasmic and cytoskeletal fractions of cultured chick myocardiocytes. The findings with sodium dodecyl sulfate-gel electrophoresis and immunoblotting showed that all three drugs modified cellular and subcellular protein levels in different ways: bezafibrate and fenofibrate produced the most significant alterations in both fractions, modifying alpha-actinin, troponin T, and tropomyosin compartmentalization in myocardiocytes, whereas gemfibrozil altered these proteins less notably. Given the role of these proteins in heart muscle contraction, Fibric Acid Derivative-induced changes may be related with the secondary effects of these drugs on heart rhythmicity.
Hirotoshi Morii - One of the best experts on this subject based on the ideXlab platform.
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Effects of lipid-lowering drugs on intermediate-density lipoprotein in uremic patients.
Kidney International, 1999Co-Authors: Yoshiki Nishizawa, Takashi Inoue, Tsutomu Tabata, Tetsuo Shoji, Hirotoshi MoriiAbstract:Effects of lipid-lowering drugs on intermediate-density lipoprotein in uremic patients Background Patients with chronic renal failure often have alterations in lipoprotein profile including elevated very-low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL), and reduced high density lipoprotein (HDL) levels. Among these changes, raised IDL has been shown as an independent risk factor for atherosclerosis in hemodialysis patients. There are a limited number of studies reporting pharmacological approaches to IDL reduction in a uremic population. Methods We therefore summarize the effects of lipid-lowering drugs on IDL levels in patients with chronic renal failure treated by hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Results First, a nicotinic Acid analog niceritrol was given to hemodialysis patients. The drug increased HDL-cholesterol by 11%, but the reductions in VLDL-, IDL- and LDL-cholesterol were not significant. Second, CAPD patients were treated with a Fibric Acid Derivative clinofibrate, which was excreted mainly into bile unlike other drugs in this class. The fibrate resulted in a remarkable reduction in VLDL-triglycerides, although it did not reduce IDL-cholesterol. Finally, an HMG-CoA reductase inhibitor (statin) pravastatin was used in HD and CAPD patients. Pravastatin reduced IDL- and LDL-cholesterol to the same extent (by 31%). None of these treatments caused serious adverse effects. Conclusions We propose that IDL is an important target in the management of uremic dyslipidemia. To date, statins have been shown to be suitable for this purpose, although it remains to be clarified whether such an intervention reduces the risk for atherosclerotic vascular events in the uremic population.
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Effects of lipid-lowering drugs on intermediate-density lipoprotein in uremic patients.
Kidney international. Supplement, 1999Co-Authors: Yoshiki Nishizawa, Takashi Inoue, Tsutomu Tabata, Tetsuo Shoji, Hirotoshi MoriiAbstract:Patients with chronic renal failure often have alterations in lipoprotein profile including elevated very-low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL), and reduced high density lipoprotein (HDL) levels. Among these changes, raised IDL has been shown as an independent risk factor for atherosclerosis in hemodialysis patients. There are a limited number of studies reporting pharmacological approaches to IDL reduction in a uremic population. We therefore summarize the effects of lipid-lowering drugs on IDL levels in patients with chronic renal failure treated by hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). First, a nicotinic Acid analog niceritrol was given to hemodialysis patients. The drug increased HDL-cholesterol by 11%, but the reductions in VLDL-, IDL- and LDL-cholesterol were not significant. Second, CAPD patients were treated with a Fibric Acid Derivative clinofibrate, which was excreted mainly into bile unlike other drugs in this class. The fibrate resulted in a remarkable reduction in VLDL-triglycerides, although it did not reduce IDL-cholesterol. Finally, an HMG-CoA reductase inhibitor (statin) pravastatin was used in HD and CAPD patients. Pravastatin reduced IDL- and LDL-cholesterol to the same extent (by 31%). None of these treatments caused serious adverse effects. We propose that IDL is an important target in the management of uremic dyslipidemia. To date, statins have been shown to be suitable for this purpose, although it remains to be clarified whether such an intervention reduces the risk for atherosclerotic vascular events in the uremic population.
Heikki M Frick - One of the best experts on this subject based on the ideXlab platform.
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a study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a Fibric Acid Derivative in men after coronary bypass surgery
Controlled Clinical Trials, 1997Co-Authors: Mikko Syvanne, Marjariitta Taskinen, Markku S Nieminen, Vesa Manninen, Antero Y Kesaniemi, Amos Pasternack, James W Nawrocki, Harry Haber, Heikki M FrickAbstract:Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged ~70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2vZ years. The lipid inclusion criteria were HDL cholesterol concentration ~1.1 mmol/L, low density lipoprotein (LDL) cholesterol ~4.5 mmol/L, and serum triglyceride ~4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index >30 kg/m*, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement
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a study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a Fibric Acid Derivative in men after coronary bypass surgery the rationale design and baseline characteristics of the locat study
Controlled Clinical Trials, 1997Co-Authors: Mikko Syvanne, Marjariitta Taskinen, Markku S Nieminen, Vesa Manninen, Antero Y Kesaniemi, Amos Pasternack, James W Nawrocki, Harry Haber, Heikki M FrickAbstract:Abstract Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged ⩽ 70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2 1 2 years. The lipid inclusion criteria were HDL cholesterol concentration ⩽ 1.1mmol/L, low density lipoprotein (LDL) cholesterol ⩽ 4.5 mmol/L, and serum triglyceride ⩽ 4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index > 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 ± 6.8 (mean ± standard deviation) years old, had a body mass index 26.4 ± 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 ± 0.64, 5.17 ± 0.64, 0.82 ± 0.14, and 3.61 ± 0.53 mmol/L, respectively.
Mikko Syvanne - One of the best experts on this subject based on the ideXlab platform.
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a study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a Fibric Acid Derivative in men after coronary bypass surgery
Controlled Clinical Trials, 1997Co-Authors: Mikko Syvanne, Marjariitta Taskinen, Markku S Nieminen, Vesa Manninen, Antero Y Kesaniemi, Amos Pasternack, James W Nawrocki, Harry Haber, Heikki M FrickAbstract:Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged ~70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2vZ years. The lipid inclusion criteria were HDL cholesterol concentration ~1.1 mmol/L, low density lipoprotein (LDL) cholesterol ~4.5 mmol/L, and serum triglyceride ~4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index >30 kg/m*, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement
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a study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a Fibric Acid Derivative in men after coronary bypass surgery the rationale design and baseline characteristics of the locat study
Controlled Clinical Trials, 1997Co-Authors: Mikko Syvanne, Marjariitta Taskinen, Markku S Nieminen, Vesa Manninen, Antero Y Kesaniemi, Amos Pasternack, James W Nawrocki, Harry Haber, Heikki M FrickAbstract:Abstract Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged ⩽ 70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2 1 2 years. The lipid inclusion criteria were HDL cholesterol concentration ⩽ 1.1mmol/L, low density lipoprotein (LDL) cholesterol ⩽ 4.5 mmol/L, and serum triglyceride ⩽ 4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index > 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 ± 6.8 (mean ± standard deviation) years old, had a body mass index 26.4 ± 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 ± 0.64, 5.17 ± 0.64, 0.82 ± 0.14, and 3.61 ± 0.53 mmol/L, respectively.
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a study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a Fibric Acid Derivative in men after coronary bypass surgery the rationale design and baseline characteristics of the locat study
Controlled Clinical Trials, 1997Co-Authors: Mikko Syvanne, Marjariitta Taskinen, Amos Pasternack, James W Nawrocki, Harry Haber, Y A Kesaniemi, M H FrickAbstract:: Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 +/- 6.8 (mean +/- standard deviation) years old, had a body mass index 26.4 +/- 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 +/- 0.64, 5.17 +/- 0.64, 0.82 +/- 0.14, and 3.61 +/- 0.53 mmol/L, respectively.