Efficacy and Safety of Ezetimibe Coadministered With Atorvastatin or Simvastatin in Patients With Homozygous Familial Hypercholesterolemia

Gagné, Claude; Gaudet, Daniel; Bruckert, Éric

doi:10.1161/01.cir.0000018744.58460.62

Cited by 435 publications

(236 citation statements)

References 33 publications

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“…3 Even in the developed countries, the data on efficacy and safety of various lipid lowering therapies is limited. 4,5,7 We did not observe statin induced myopathy in our patients although a recent Indian study shows that 7.5% of adult statin users developed myopathy.…”

Section: Discussioncontrasting

confidence: 69%

“…5 In this context, our experience is similar to studies in patients with HeFH which showed LDL-C reductions of upto 55% with maximally tolerated doses of combinations of statins and ezetimibe. [4][5][6][7] Further reductions in plasma lipid concentrations are possible with LDL apheresis which is widely practiced in developed countries but has only recently been conducted successfully in India. 8 The increase in HDL-C achieved in our patients was more as compared to previous studies (29.7% versus 5-10 %).…”

Section: Discussionmentioning

confidence: 99%

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Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

Dayal

Seetharaman

Bhunwal

et al. 2017

Int J Contemp Pediatr

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Background: Homozygous familial hypercholesterolemia (HoFH) is an underdiagnosed and undertreated genetic disorder of lipoprotein metabolism associated with mortality during young age due to accelerated atherosclerosis. There is limited data on the efficacy of lipid lowering therapies in HoFH. Methods: Medical records of 3 children with HoFH who received a combination of atorvastatin and ezetimibe for a mean duration of 11.6±1.5 years were retrospectively analysed. Results: There was a significant decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) from the baseline levels (mean percent change in TC, LDL-C, TG and HDL-C of 58.5%, 56.2%, 67.5% and 29.7% respectively). Conclusions: We conclude that long-term use of a combination of atorvastatin and ezetimibe significantly lowers the plasma LDL-C concentrations in patients with HoFH without causing any significant adverse effects. Ours is the first study from India on long-term use of lipid modifying drug therapy in children with HoFH.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

Dayal

Seetharaman

Bhunwal

et al. 2017

Int J Contemp Pediatr

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“…Одним из препаратов этого класса является АМG145 (эволукумаб). В двойном слепом исследовании продемонстрировано, что эво-лукумаб эффективно снижает уровень холестерина ЛПНП у пациентов с гетерозиготной гиперхолесте-ринемией в случае, если комбинированная терапия статинами и эзетролом не позволяет достичь целевого уровня холестерина [28]. В исследованиях по приме-нению эволукумаба для лечения гомозиготной ги-перхолестеринемии показано, что препарат снижает уровень холестерина ЛПНП только у «рецептор-де-фектных» пациентов [29,30].…”

Section: лечениеunclassified

Modern Approaches to the Treatment of Homozygous Familial Hypercholesterolemia

Леонтьева¹

2017

Ross. vestn. perinatol. pediatr.

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“…38 The finding that ezetimibe lowers LDL-C levels in subjects with homozygous familial hypercholesterolemia indicates that the rate of production of LDL may fall in response to the reduction in cholesterol absorption. 39 The extent to which the LDL-C-lowering effect of ezetimibe may also reflect upregulation of hepatic LDL receptor activity has not been determined. Ezetimibe blocks the absorption of cholesterol and plant sterols, but does not affect the absorption of bile acids, fatty acids, fat soluble vitamins, or triglycerides.…”

Section: Ezetimibe a Novel Potent And Specific Cholesterol Absorptmentioning

confidence: 99%

Cholesterol metabolism and therapeutic targets: Rationale for targeting multiple metabolic pathways

Turley

2004

Clin Cardiol

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The liver is the major regulator of the plasma low density lipoprotein cholesterol (LDL‐C) concentration because it is not only the site of formation of very low density lipoproteins (VLDL), the precursors of most LDL in the circulation, but it is also the organ where the bulk of receptor‐mediated clearance of LDL takes place. The liver also initially clears all the cholesterol that is absorbed from the small intestine. The absorption of excess cholesterol can potentially increase the amount of cholesterol stored in the liver. This, in turn, can result in increased VLDL secretion, and hence LDL formation, and also downregulation of hepatic LDL receptor activity. Such events will potentially increase plasma LDL‐C levels. The converse situation occurs when cholesterol absorption is inhibited. Cholesterol enters the lumen of the small intestine principally from bile and diet. The major steps involved in the absorption process have been characterized. On average, about half of all cholesterol entering the intestine is absorbed, but the fractional absorption rate varies greatly among individuals. While the basis for this variability is not understood, it may partly explain why some patients respond poorly or not at all to statins and other classes of lipid‐lowering drugs. There are few data relating to racial differences in cholesterol absorption. One study reported a significantly higher rate in African Americans compared with non‐African Americans. Multiple lipid‐lowering drugs that target pathways involving the absorption, synthesis, transport, storage, catabolism, and excretion of cholesterol are available. Ezetimibe selectively blocks cholesterol absorption and lowers plasma LDL‐C levels by an average of 18%. When ezetimibe is coadministered with lower doses of statins, there is an additive reduction in LDL‐C level, which equals the reduction achieved with maximal doses of statins alone. Dual inhibition of cholesterol synthesis and absorption is an effective new strategy for treating hypercholesterolemia.

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Efficacy and Safety of Ezetimibe Coadministered With Atorvastatin or Simvastatin in Patients With Homozygous Familial Hypercholesterolemia

Cited by 435 publications

References 33 publications

Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

Modern Approaches to the Treatment of Homozygous Familial Hypercholesterolemia

Cholesterol metabolism and therapeutic targets: Rationale for targeting multiple metabolic pathways

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