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Bart Staels - One of the best experts on this subject based on the ideXlab platform.
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Fibrates suppress bile acid synthesis via peroxisome proliferator activated receptor α mediated downregulation of cholesterol 7α hydroxylase and sterol 27 hydroxylase expression
Arteriosclerosis Thrombosis and Vascular Biology, 2001Co-Authors: S M Post, Bart Staels, Helene Duez, Philippe Gervois, Folkert Kuipers, H M G PrincenAbstract:Fibrates are hypolipidemic drugs that affect the expression of genes involved in lipid metabolism by activating peroxisome proliferator-activated receptors (PPARs). Fibrate treatment causes adverse changes in biliary lipid composition and decreases bile acid excretion, leading to an increased incidence of cholesterol gallstones. In this study, we investigated the effect of Fibrates on bile acid synthesis. CiproFibrate and the PPARalpha agonist Wy14,643 decreased bile acid synthesis in cultured rat hepatocytes and suppressed cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities, paralleled by a similar reduction of the respective mRNAs. Treatment of rats with 0.05% (wt/wt) ciproFibrate decreased cholesterol 7alpha-hydroxylase enzyme activity and mRNA. The functional involvement of PPARalpha in the suppression of both enzymes was proven with the use of PPARalpha-null mice. In wild-type mice, ciproFibrate reduced cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase enzyme activities and mRNA. The decrease in mRNA of both enzymes is regulated transcriptionally and posttranscriptionally, respectively, resulting in a decline in the output of fecal bile acids (-45%) and a 3-fold increase in fecal cholesterol secretion. These effects were completely abolished in PPARalpha-null mice. A decreased bile acid production by PPARalpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase may contribute to the increased risk of gallstone formation after Fibrate treatment.
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peroxisome proliferator activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross talk with transcription factors nf kappab and ap 1
Journal of Biological Chemistry, 1999Co-Authors: Philippe Delerive, Jean-charles Fruchart, Karolien De Bosscher, Sandrine Besnard, Wim Vanden Berghe, Jeffrey M Peters, Frank J Gonzalez, Alain Tedgui, Guy Haegeman, Bart StaelsAbstract:Interleukin-6 (IL-6) is a pleiotropic cytokine, whose plasma levels are elevated in inflammatory diseases such as atherosclerosis. We have previously reported that peroxisome proliferator-activated receptor alpha (PPARalpha) ligands (Fibrates) lower elevated plasma concentrations of IL-6 in patients with atherosclerosis and inhibit IL-1-stimulated IL-6 secretion by human aortic smooth muscle cells (SMC). Here, we show that aortic explants isolated from PPARalpha-null mice display an exacerbated response to inflammatory stimuli, such as lipopolysaccharide (LPS), as demonstrated by increased IL-6 secretion. Furthermore, Fibrate treatment represses IL-6 mRNA levels in LPS-stimulated aortas of PPARalpha wild-type, but not of PPARalpha-null mice, demonstrating a role for PPARalpha in this Fibrate action. In human aortic SMC, Fibrates inhibit IL-1-induced IL-6 gene expression. Furthermore, activation of PPARalpha represses both c-Jun- and p65-induced transcription of the human IL-6 promoter. Transcriptional interference between PPARalpha and both c-Jun and p65 occurs reciprocally, since c-Jun and p65 also inhibit PPARalpha-mediated activation of a PPAR response element-driven promoter. This transcriptional interference occurs independent of the promoter context as demonstrated by cotransfection experiments using PPARalpha, p65, and c-Jun Gal4 chimeras. Overexpression of the transcriptional coactivator cAMP-responsive element-binding protein-binding protein (CBP) does not relieve PPARalpha-mediated transcriptional repression of p65 and c-Jun. Finally, glutathione S-transferase pull-down experiments demonstrate that PPARalpha physically interacts with c-Jun, p65, and CBP. Altogether these data indicate that Fibrates inhibit the vascular inflammatory response via PPARalpha by interfering with the NF-kappaB and AP-1 transactivation capacity involving direct protein-protein interaction with p65 and c-Jun.
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peroxisome proliferator activated receptor α negatively regulates the vascular inflammatory gene response by negative cross talk with transcription factors nf κb and ap 1
Journal of Biological Chemistry, 1999Co-Authors: Philippe Delerive, Jean-charles Fruchart, Karolien De Bosscher, Sandrine Besnard, Wim Vanden Berghe, Jeffrey M Peters, Frank J Gonzalez, Alain Tedgui, Guy Haegeman, Bart StaelsAbstract:Abstract Interleukin-6 (IL-6) is a pleiotropic cytokine, whose plasma levels are elevated in inflammatory diseases such as atherosclerosis. We have previously reported that peroxisome proliferator-activated receptor α (PPARα) ligands (Fibrates) lower elevated plasma concentrations of IL-6 in patients with atherosclerosis and inhibit IL-1-stimulated IL-6 secretion by human aortic smooth muscle cells (SMC). Here, we show that aortic explants isolated from PPARα-null mice display an exacerbated response to inflammatory stimuli, such as lipopolysaccharide (LPS), as demonstrated by increased IL-6 secretion. Furthermore, Fibrate treatment represses IL-6 mRNA levels in LPS-stimulated aortas of PPARα wild-type, but not of PPARα-null mice, demonstrating a role for PPARα in this Fibrate action. In human aortic SMC, Fibrates inhibit IL-1-induced IL-6 gene expression. Furthermore, activation of PPARα represses both c-Jun- and p65-induced transcription of the human IL-6 promoter. Transcriptional interference between PPARα and both c-Jun and p65 occurs reciprocally, since c-Jun and p65 also inhibit PPARα-mediated activation of a PPAR response element-driven promoter. This transcriptional interference occurs independent of the promoter context as demonstrated by cotransfection experiments using PPARα, p65, and c-Jun Gal4 chimeras. Overexpression of the transcriptional coactivator cAMP-responsive element-binding protein-binding protein (CBP) does not relieve PPARα-mediated transcriptional repression of p65 and c-Jun. Finally, glutathione S-transferase pull-down experiments demonstrate that PPARα physically interacts with c-Jun, p65, and CBP. Altogether these data indicate that Fibrates inhibit the vascular inflammatory response via PPARα by interfering with the NF-κB and AP-1 transactivation capacity involving direct protein-protein interaction with p65 and c-Jun.
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mechanism of action of Fibrates on lipid and lipoprotein metabolism
Circulation, 1998Co-Authors: Bart Staels, Johan Auwerx, Jean Dallongeville, Kristina Schoonjans, Eran Leitersdorf, J C FruchartAbstract:Treatment with Fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations. Recent investigations indicate that the effects of Fibrates are mediated, at least in part, through alterations in transcription of genes encoding for proteins that control lipoprotein metabolism. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). The PPAR-alpha form mediates Fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II. Fibrates lower hepatic apoC-III production and increase lipoprotein lipase--mediated lipolysis via PPAR. Fibrates stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the beta-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production. In summary, both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of Fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.
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Mechanisms of the hypolipidemic action of Fibrates
Medical Science Symposia Series, 1998Co-Authors: Johan Auwerx, Jean Dallongeville, Jean-charles Fruchart, Bart StaelsAbstract:Fibrates are generally effective in lowering elevated plasma triglycerides and cholesterol. The magnitude of lipid changes depends however upon the patients’ pretreatment lipoprotein status [1],as well as upon the unique properties of each Fibrate. The most pronounced effects of Fibrates are a decrease in plasma triglyceride-rich lipoproteins and an increase in high density lipoprotein cholesterol (HDL-C) levels when baseline plasma concentrations are low [1]. The changes in the different lipoprotein fractions are reflected by changes in the concentrations of their major apolipoproteins. Fibrates efficiently reduce the apo C-III-containing particles of this lipoprotein class, which may be markers for increased risk for atherogenesis [2].
Jun Yong Park - One of the best experts on this subject based on the ideXlab platform.
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additional Fibrate treatment in udca refractory pbc patients
Liver International, 2019Co-Authors: Sung Won Chung, Jeong-hoon Lee, Minseok Albert Kim, Galam Leem, Sun Woong Kim, Young Chang, Hyo Young Lee, Jun Sik Yoon, Jun Yong ParkAbstract:BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although Fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of Fibrate on clinical outcomes of UDCA-refractory PBC. METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional Fibrate treatment of 160 mg/d fenoFibrate or 400 mg/d bezaFibrate (the Fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the Fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the Fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the Fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the Fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). CONCLUSIONS In patients with UDCA-refractory PBC, additional Fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.
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Additional Fibrate treatment in UDCA-refractory PBC patients.
Liver international : official journal of the International Association for the Study of the Liver, 2019Co-Authors: Sung Won Chung, Jeong-hoon Lee, Minseok Albert Kim, Galam Leem, Sun Woong Kim, Young Chang, Hyo Young Lee, Jun Sik Yoon, Jun Yong Park, Yun Bin LeeAbstract:BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although Fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of Fibrate on clinical outcomes of UDCA-refractory PBC. METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional Fibrate treatment of 160 mg/d fenoFibrate or 400 mg/d bezaFibrate (the Fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the Fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P
Jun Sik Yoon - One of the best experts on this subject based on the ideXlab platform.
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additional Fibrate treatment in udca refractory pbc patients
Liver International, 2019Co-Authors: Sung Won Chung, Jeong-hoon Lee, Minseok Albert Kim, Galam Leem, Sun Woong Kim, Young Chang, Hyo Young Lee, Jun Sik Yoon, Jun Yong ParkAbstract:BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although Fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of Fibrate on clinical outcomes of UDCA-refractory PBC. METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional Fibrate treatment of 160 mg/d fenoFibrate or 400 mg/d bezaFibrate (the Fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the Fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the Fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the Fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the Fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). CONCLUSIONS In patients with UDCA-refractory PBC, additional Fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.
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Additional Fibrate treatment in UDCA-refractory PBC patients.
Liver international : official journal of the International Association for the Study of the Liver, 2019Co-Authors: Sung Won Chung, Jeong-hoon Lee, Minseok Albert Kim, Galam Leem, Sun Woong Kim, Young Chang, Hyo Young Lee, Jun Sik Yoon, Jun Yong Park, Yun Bin LeeAbstract:BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although Fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of Fibrate on clinical outcomes of UDCA-refractory PBC. METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional Fibrate treatment of 160 mg/d fenoFibrate or 400 mg/d bezaFibrate (the Fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the Fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P
Sung Won Chung - One of the best experts on this subject based on the ideXlab platform.
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additional Fibrate treatment in udca refractory pbc patients
Liver International, 2019Co-Authors: Sung Won Chung, Jeong-hoon Lee, Minseok Albert Kim, Galam Leem, Sun Woong Kim, Young Chang, Hyo Young Lee, Jun Sik Yoon, Jun Yong ParkAbstract:BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although Fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of Fibrate on clinical outcomes of UDCA-refractory PBC. METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional Fibrate treatment of 160 mg/d fenoFibrate or 400 mg/d bezaFibrate (the Fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the Fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the Fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the Fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the Fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). CONCLUSIONS In patients with UDCA-refractory PBC, additional Fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.
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Additional Fibrate treatment in UDCA-refractory PBC patients.
Liver international : official journal of the International Association for the Study of the Liver, 2019Co-Authors: Sung Won Chung, Jeong-hoon Lee, Minseok Albert Kim, Galam Leem, Sun Woong Kim, Young Chang, Hyo Young Lee, Jun Sik Yoon, Jun Yong Park, Yun Bin LeeAbstract:BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although Fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of Fibrate on clinical outcomes of UDCA-refractory PBC. METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method. RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional Fibrate treatment of 160 mg/d fenoFibrate or 400 mg/d bezaFibrate (the Fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the Fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P
Terry A. Jacobson - One of the best experts on this subject based on the ideXlab platform.
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Myopathy with statin–Fibrate combination therapy: clinical considerations
Nature Reviews Endocrinology, 2009Co-Authors: Terry A. JacobsonAbstract:Statin–Fibrate combination regimens might be useful for patients with insulin resistance and certain types of dyslipidemia; however, the safety and efficacy of such therapy have not been systematically evaluated Risk factors of statin–Fibrate-related myopathy include advanced age, female gender, low BMI, renal disease, diabetes mellitus, hypothyroidism, multisystem disease, fever, surgery, trauma, and strenuous physical exercise The likelihood and/or severity of myopathy also depend on pharmacologic properties of the statin and the Fibrate, such as their enzymatic metabolism or excretion and/or their protein-regulated intercellular transport FenoFibrate or fenofibric acid may be Fibrates of choice for statin–Fibrate therapy because, according to pharmacokinetic and postmarketing data, they are associated with lower risks of myopathy (versus gemfibrozil) Many patients who receive statin therapy for hyperlipidemia—such as patients with diabetes mellitus and metabolic syndrome—have residual cardiovascular risk. These patients often have dyslipidemia, including low levels of HDL cholesterol and elevated levels of triglycerides and small, dense LDL. For such patients, combination treatment with statins and Fibrates is a potentially useful strategy to improve lipid and lipoprotein profiles and reduce cardiovascular risk. However, statin–Fibrate combination regimens have potential adverse effects on skeletal muscle, including myopathy. To date, no large-scale, prospective, randomized, controlled trial has evaluated the safety and efficacy of statin–Fibrate combination therapy; one such trial is underway but will not report data until 2010. Until then, clinicians need to consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic and other factors that can increase the systemic exposure of statins and/or Fibrates and hence heighten the risk of toxic effects on muscles, as well as data from clinical trials and recommendations of consensus panels to optimize the safety of such combination regimens. On the basis of currently available data, fenoFibrate or fenofibric acid is the Fibrate of choice when used in combination with a statin because each is, in theory, associated with a lower risk of myopathy than gemfibrozil. When patients treated with HMG-CoA reductase inhibitors exhibit residual risk—including low levels of high-density lipoprotein cholesterol and elevated triglycerides—adjunctive therapy with a fibric-acid derivative (i.e. Fibrate) may be appropriate. However, given the prospect of statin–Fibrate-associated myopathy, major factors affecting the question of which Fibrate to choose in this setting have not been systematically evaluated. This article discusses available pharmacokinetic, pharmacodynamic, clinical pharmacologic, and postmarketing surveillance issues that may inform such decision making.
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Myopathy with statin-Fibrate combination therapy: clinical considerations.
Nature reviews. Endocrinology, 2009Co-Authors: Terry A. JacobsonAbstract:Many patients who receive statin therapy for hyperlipidemia-such as patients with diabetes mellitus and metabolic syndrome--have residual cardiovascular risk. These patients often have dyslipidemia, including low levels of HDL cholesterol and elevated levels of triglycerides and small, dense LDL. For such patients, combination treatment with statins and Fibrates is a potentially useful strategy to improve lipid and lipoprotein profiles and reduce cardiovascular risk. However, statin-Fibrate combination regimens have potential adverse effects on skeletal muscle, including myopathy. To date, no large-scale, prospective, randomized, controlled trial has evaluated the safety and efficacy of statin-Fibrate combination therapy; one such trial is underway but will not report data until 2010. Until then, clinicians need to consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic and other factors that can increase the systemic exposure of statins and/or Fibrates and hence heighten the risk of toxic effects on muscles, as well as data from clinical trials and recommendations of consensus panels to optimize the safety of such combination regimens. On the basis of currently available data, fenoFibrate or fenofibric acid is the Fibrate of choice when used in combination with a statin because each is, in theory, associated with a lower risk of myopathy than gemfibrozil.
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Fibrates in Combination With Statins in the Management of Dyslipidemia
Journal of clinical hypertension (Greenwich Conn.), 2006Co-Authors: Terry A. Jacobson, Franklin H. ZimmermanAbstract:While elevated low-density lipoprotein cholesterol is the primary target of hypercholesterolemia treatment, high triglycerides and low high-density lipoprotein cholesterol are also important targets for therapy. Correcting these lipid abnormalities should be an integral part of therapy in hypertensive individuals. Medications such as the Fibrates are effective and well tolerated for reducing triglycerides and increasing high-density lipoprotein cholesterol, and their use has resulted in a reduction in cardiovascular events. Fibrates are also recommended as adjunct therapy for patients receiving statins whose low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol is not reduced to goal levels. The combination of a statin and a Fibrate may, however, raise the risk of myopathy and rhabdomyolysis. Gemfibrozil, one of the Fibrates, but not fenoFibrate, interferes with statin glucuronidation, which may increase the risk of myopathy due to elevations in statin serum levels. This may at least partially explain the lower incidence of myopathy with fenoFibrate compared with gemfibrozil when combined with statins. Combination therapy with a Fibrate and a statin is a potentially useful therapy for patients with atherogenic lipid profiles, for which fenoFibrate appears to be a more appropriate choice due to less myopathic potential.