Micronised fenofibrate or gemfibrozil in patients with combined hyperlipidaemia: A double-blind randomised multicentre trial

Džavík, Vladimir; Ansquer, J.-C.; Delaval, D.

doi:10.1016/s0021-9150(99)80119-1

Cited by 4 publications

(3 citation statements)

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“…Fibrates primarily reduce triglycerides (TG) and increase high density lipoprotein cholesterol (HDLC) levels with variable effects on LDLC [ 23 ]. Using samples from a study that compared the efficacy of two standard fibrate therapies [ 24 ], we measured plasma PCSK9 levels from 19 individuals (12 men and 7 women) pre- and post-fibrate treatment. We did not observe any significant difference in pre-treatment lipids between the fenofibrate (n = 9) and gemfibrozil (n = 10) groups or in lipoprotein parameters in response to treatments between the two groups (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…For human studies described below all 59 subjects gave informed written consent and the ethics research committees approved study protocols. The fibrate treatment group included 19 subjects (12 males and 7 females) from a post-hoc study who were recruited from the Ottawa Hospital Lipid Clinic and given fibrate therapy [ 24 ]. Subjects were required to have a TC/HDLC ratio ≥ 6.0 for males, 5.6 for females and elevated TGs (2.3–5.5 mmol/L).…”

Section: Methodsmentioning

confidence: 99%

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Plasma PCSK9 levels are significantly modified by statins and fibrates in humans

et al. 2008

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BackgroundProprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.ResultsHerein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6× vs 1.5×, respectively at 10 μM), while fenofibrate did not induce changes in either.ConclusionThese results suggest that in vivo (1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Plasma PCSK9 levels are significantly modified by statins and fibrates in humans

et al. 2008

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“…[39] • • In 234 patients with mixed hyperlipidemia (baseline TC to HDL-C ratio ≥5.6 and TG level of 2.2 to 5.6 mmol/L), there was no statistically significant difference between the increases in HDL-C levels produced by fenofibrate 200mg once daily and gemfibrozil 1200mg once daily for 24 weeks (16.0 and 11.8%, respectively, from 0.9 mmol/L at baseline). [39] • • In 234 patients with mixed hyperlipidemia (baseline TC to HDL-C ratio ≥5.6 and TG level of 2.2 to 5.6 mmol/L), there was no statistically significant difference between the increases in HDL-C levels produced by fenofibrate 200mg once daily and gemfibrozil 1200mg once daily for 24 weeks (16.0 and 11.8%, respectively, from 0.9 mmol/L at baseline).…”

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confidence: 96%

Micronized Fenofibrate in Dyslipidemia

Sharpe¹,

Ormrod²,

Jarvis³

2002

American Journal of Cardiovascular Drugs

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The prodrug fenofibrate, a synthetic phenoxy-isobutyric acid derivative, is rapidly hydrolyzed in vivo to form fenofibric acid, which alters plasma lipid levels by activating the peroxisome proliferator-activated receptor alpha. The micronized fenofibrate 200 mg capsule formulation, and the recently developed micronized fenofibrate 160 mg tablet formulation, are bioequivalent. Micronized fenofibrate 200 mg/day (capsules) increased high density lipoprotein cholesterol (HDL-C) levels significantly from baseline in up to 7098 patients with various dyslipidemias in noncomparative studies. Micronized fenofibrate 200 mg/day (capsules) produced significantly greater elevations in HDL-C levels than a variety of HMG-CoA reductase inhibitors in small, randomized, double-blind and nonblind studies in patients with dyslipidemia (n = 91 to 227). This formulation of fenofibrate and gemfibrozil produced similar increases in HDL-C levels in a randomized, double-blind study (n = 234). Micronized fenofibrate 160 mg once daily (tablet) increased HDL-C levels significantly from baseline by 10.6 to 14.5% in patients with type IIa or IIb dyslipidemia (n = 353) in two noncomparative studies. Additionally, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and LDL-C to HDL-C and TC to HDL-C ratios were lowered significantly from baseline. The tablet and capsule formulations of fenofibrate were both generally well tolerated in two noncomparative studies in 375 or 9884 patients. In double-blind, placebo-controlled trials in a total of 804 patients, the pooled incidences of individual adverse events were generally similar with fenofibrate and placebo.

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Effect of fibrates on postprandial remnant-like particles in patients with combined hyperlipidemia

et al. 2004

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Micronised fenofibrate or gemfibrozil in patients with combined hyperlipidaemia: A double-blind randomised multicentre trial

Cited by 4 publications

References 0 publications

Plasma PCSK9 levels are significantly modified by statins and fibrates in humans

Plasma PCSK9 levels are significantly modified by statins and fibrates in humans

Micronized Fenofibrate in Dyslipidemia

Effect of fibrates on postprandial remnant-like particles in patients with combined hyperlipidemia

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