Safety and Efficacy of Long-Term Co-Administration of Fenofibrate and Ezetimibe in Patients With Mixed Hyperlipidemia

McKenney, James M.; Farnier, Michel; Lo, Kwok-Wing; Bays, Harold; Perevozkaya, Inna; Carlson, Gary; Davies, Michael J.; Mitchel, Yale; Gumbiner, Barry M.

doi:10.1016/j.jacc.2005.11.072

Cited by 96 publications

(71 citation statements)

References 9 publications

(12 reference statements)

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“…49 A combination of fenofibrate and ezetimibe was recently shown to be safe and effective for patients with elevated triglyceride and LDL-C levels. 50 Canada recently joined the United States in approving this combination for therapeutic use.…”

Section: Other Lipid-lowering Medicationsmentioning

confidence: 99%

Hypertriglyceridemia: its etiology, effects and treatment

Yuan¹,

Alshali²,

Hegele³

2007

Canadian Medical Association Journal

495

396

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Section: Other Lipid-lowering Medicationsmentioning

confidence: 99%

Hypertriglyceridemia: its etiology, effects and treatment

Yuan¹,

Alshali²,

Hegele³

2007

Canadian Medical Association Journal

495

396

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“…In the last decade, statins (HMG-CoA reductase inhibitors) have become the drug of choice for the treatment of dyslipidemia [36][37][38].…”

Section: Lipid-lowering Drugsmentioning

confidence: 99%

Microsomal Transfer Protein Inhibitors, New Approach for Treatment of Familial Hypercholesterolemia, Review of the Literature, Original Findings, and Clinical Significance

Kolovou

Vasiliadis

Gontoras

et al. 2015

Cardiovascular Therapeutics

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SUMMARYThe genetic causes of cholesterol metabolism disorders usually lead to premature atherosclerosis. The most well recognized genetically caused hypercholesterolemia is familial hypercholesterolemia. Although the disease is well known, as the discovery of low-density lipoprotein receptor, the classical treatment with lipid-lowering drugs (statins, fibrates, ezetimibe, colesevelam) is still not adequate and new options are seeking. This review is an attempt to analyze the microsomal transfer protein (MTP) inhibitors as a new approach for treatment of familial hypercholesterolemia, to reviews the literature according to MTP inhibitors and finally to provide original findings.

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“…The effects of combining ezetimibe with fenofibrate on atherogenic lipid profile have also been evaluated 42,43) . In a multicenter, double-blind, randomized trial, 625 patients with mixed hyperlipidemia (LDL-C 130-220 mg/dL, TG 150-500 mg/dL), were randomized in a 3:3:3:1 ratio to one of 4 treatments for 12 weeks: ezetimibe 10 mg, fenofibrate 160 mg, fenofibrate 160 mg plus ezetimibe 10 mg, and placebo 42) .…”

Section: Ezetimibe and Ezetimibe/simvastatin In Combination With Fenomentioning

confidence: 99%

“…In a multicenter, double-blind, randomized trial, 625 patients with mixed hyperlipidemia (LDL-C 130-220 mg/dL, TG 150-500 mg/dL), were randomized in a 3:3:3:1 ratio to one of 4 treatments for 12 weeks: ezetimibe 10 mg, fenofibrate 160 mg, fenofibrate 160 mg plus ezetimibe 10 mg, and placebo 42) . After completing the 12-week study, 576 patients continued into a double-blind, 48-week extension phase comparing fenofibrate (n 236) to fenofibrate plus ezetimibe (n 340) 43) Patients in the fenofibrate plus ezetimibe and fenofibrate groups continued on their respective previous treatment, and patients in the ezetimibe and placebo groups were switched to fenofibrate plus ezetimibe and fenofibrate, respectively. The fenofibrate plus ezetimibe produced significantly greater reductions in LDL-C compared with fenofibrate ( 22% vs 9%, respectively; p 0.001).…”

Section: Ezetimibe and Ezetimibe/simvastatin In Combination With Fenomentioning

confidence: 99%

Zetia: Inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to Reduce Intestinal Cholesterol Absorption and Treat Hyperlipidemia

Davis¹,

Veltri²

2007

J Atheroscler Thromb

143

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Zetia (ezetimibe) is a selective cholesterol absorption inhibitor, which potently inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides or bile acids. Ezetimibe reduces the small intestinal enterocyte uptake and absorption of cholesterol by binding to Niemann-Pick C1 Like 1 (NPC1L1), which keeps cholesterol in the intestinal lumen for excretion. Ezetimibe undergoes glucuronidation to a single metabolite and localizes at the intestinal wall, where it binds with higher affinity for NPC1L1 than ezetimibe to prevent cholesterol absorption. Enterohepatic recirculation of ezetimibe and/or its glucuronide ensures repeated delivery to the intestinal site of action and limited peripheral exposure. Ezetimibe has no effect on the activity of major drug metabolizing enzymes (CYP450), which reduces any potential drug-drug interactions with other medications. Ezetimibe (10 mg/day) was found to inhibit cholesterol absorption by an average of 54% in hypercholesterolemic individuals and by 58% in vegetarians. Ezetimibe alone reduced plasma total and LDL-Cholesterol (18%) levels in patients with primary hypercholesterolemia. When ezetimibe was added to on-going statin treatment, an additional 25% reduction in LDL-C was found in patients with primary hypercholesterolemia and an additional 21% reduction in LDL-C in homozygous familial hypercholesterolemia. Ezetimibe in combination with statins produces additional reductions in plasma cholesterol levels and allows for more patients to achieve their LDL-C goals. . Zetia was identified through the characterization of the active biliary metabolites of its predecessor, SCH 48461, and extensive structure-activity relationship information obtained from a seven day cholesterol-fed hamster model 2) . Ezetimibe dose-dependently inhibited diet-induced hypercholesterolemia in hamsters with an ED50 of 0.04 mg/kg. In an acute model of intestinal absorption using radiolabeled cholesterol in rats, ezetimibe inhibited the appearance of radiolabeled cholesterol in plasma with an ED50 of 0.0015 mg/kg ninety minutes after dosing, indicating that the onset of activity was rapid 3) . Ezetimibe has proven to be most potent pre-clinically in cholesterol-fed rhesus monkeys with an ED50 0.0005 mg/kg/day. A single dose of the ezetimibe analog, SCH 48461, administered to cynomolgus monkeys fed a single cholesterol-containing meal caused a significant reduction of cholesterol in chylomicrons and chylomicron remnants during the postprandial phase without affecting triglyceride content 4) . Ezetimibe selectively inhibits the transport of cholesterol across the intestinal wall. Ezetimibe does not affect intestinal cholesteryl ester hydrolysis and the absorption of fatty acids thus generated. The free cholesterol from this hydrolysis, however, was not absorbed J Atheroscler

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Safety and Efficacy of Long-Term Co-Administration of Fenofibrate and Ezetimibe in Patients With Mixed Hyperlipidemia

Abstract: Long-term, 48-week co-administration of FENO plus EZE was well tolerated and more efficacious than FENO in patients with mixed hyperlipidemia.

Cited by 96 publications

References 9 publications

Hypertriglyceridemia: its etiology, effects and treatment

Hypertriglyceridemia: its etiology, effects and treatment

Microsomal Transfer Protein Inhibitors, New Approach for Treatment of Familial Hypercholesterolemia, Review of the Literature, Original Findings, and Clinical Significance

Zetia: Inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to Reduce Intestinal Cholesterol Absorption and Treat Hyperlipidemia

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