The effect of orlistat and ezetimibe, alone or in combination, on serum LDL and small dense LDL cholesterol levels in overweight and obese patients with hypercholesterolaemia

Nakou, Eleni; Filippatos, Theodosios D.; Georgoula, M.; Kiortsis, Dimitrios N.; Tselepis, Alexandros D.; Mikhailidis, Dimitri P.; Elisaf, Moses

doi:10.1185/03007990802177150

Cited by 67 publications

(65 citation statements)

References 52 publications

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“…Given the potency of ezetimibe to effectively reduce LDL-C levels, the possible pleiotropic antiatherosclerotic actions of ezetimibe have been posed under question [12]. Several studies have come with contradictory results with regard to the effect of ezetimibe on inflammatory markers and endothelial function indices [12,26,27]. The anti-oxidative potential of this drug is also under consideration.…”

Section: Discussionmentioning

confidence: 96%

Ezetimibe Treatment Lowers Indicators of Oxidative Stress in Hypercholesterolemic Subjects with High Oxidative Stress

Kostapanos

Spyrou

Tellis

et al. 2011

Lipids

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Ezetimibe effectively reduces low-density lipoprotein cholesterol (LDL-C). In this study, we tested the hypothesis that ezetimibe monotherapy may also decrease markers of oxidative stress in subjects with hypercholesterolemia. Subjects with hypercholesterolemia and no evidence of cardiovascular disease were randomly allocated to open-label ezetimibe monotherapy 10 mg/day (EZT group) or therapeutic lifestyle changes (TLC group). At baseline and 12 weeks post-treatment serum lipoprotein and apolipoprotein levels as well as oxidative stress parameters, including oxidized LDL (ox-LDL), 8-isoprostanes (8-epiPGF2a) and reactive oxygen metabolites (d-ROMs) levels, were blindly determined. A total of 60 patients were included; 30 in each group. Despite a significant decrease in ox-LDL levels (by 20.8%, p < 0.001 vs. baseline; p < 0.001 vs. TLC group) in the EZT group no change in the ratio ox-LDL to LDL-C was noticed following ezetimibe treatment. No significant change in 8-epiPGF2a and d-ROMs levels was observed in the EZT group. Of note, a significant decrease in 8-epiPGF2a and d-ROMs levels (by 20.4% and 18.2%, respectively, p < 0.01 vs. baseline for both), was noted among patients in the EZT group who exhibited 'high oxidative stress' at baseline. No change in any of oxidative stress parameters was noted in the TLC group. Ezetimibe may decrease markers of oxidative stress in hypercholesterolemic subjects. This benefit may be more profound among patients who exhibit 'high oxidative stress' at baseline.

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Section: Discussionmentioning

confidence: 96%

Ezetimibe Treatment Lowers Indicators of Oxidative Stress in Hypercholesterolemic Subjects with High Oxidative Stress

Kostapanos

Spyrou

Tellis

et al. 2011

Lipids

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“…Furthermore, orlistat, alone or in combination with ezetimibe, improved several anthropometric and metabolic variables. 34 …”

Section: Treatmentmentioning

confidence: 99%

Effect of body weight loss and normalization on blood pressure in overweight non-obese patients with stage 1 hypertension

et al. 2010

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We evaluated the effects of body weight (BW) loss on blood pressure (BP) in overweight non-obese patients with stage 1 hypertension. We enrolled 376 overweight (body mass index (BMI) X25 and o30 kg m À2 ) stage 1 hypertensive patients in this prospective 12-month trial. Each patient received tailored, low caloric dietary advice. After 6 months, patients with a BW reduction o5% were excluded. Body weight, BMI, BP, fasting plasma glucose (FPG), fasting plasma insulin (FPI), leptin (pL), renin and aldosterone levels were evaluated at baseline and after 6 and 12 months. In 222 patients who completed the study, a mean weight reduction of 8.1 kg reduced systolic blood pressure (SBP) by 4.2 mm Hg and diastolic blood pressure (DBP) by 3.3 mm Hg (Po0.05), which was accompanied by a significant decrease in FPI, pL and aldosterone levels (Po0.05). Larger SBP/DBP reductions were observed in 106 patients with normalized BMI (À5/À4.5 mm Hg, Po0.01) compared with the 116 patients who did not become normalized (À3.3/À1.6 mm Hg). The former also presented with greater decreases in FPG, FPI, pL, renin and aldosterone levels. Of the 106 patients who had normalized BMI, 52 also had normalized BP. Clinical and metabolic characteristics of these patients were similar to those of the 56 patients who did not have normalized BP. In overweight, mild hypertensive patients, weight loss was effective in reducing BP and in reversing some endocrinologic alterations associated with being overweight. Half of the patients who had normalized BMI also had normalized BP, which could indicate that these patients essentially did not have a form of hypertension but that these effects were instead secondary to being overweight. Keywords: blood pressure; overweight; weight-loss INTRODUCTION Excessive body weight (BW), in particular abdominal obesity, increases the risk for cardiovascular disease, stroke, type 2 diabetes, hypertension, lipoprotein disorders, osteoarthritis, certain types of cancers and total mortality. 1-5 An escalating epidemic of overweight (body mass index (BMI) X25 and o30 kg m À2 ) and obesity (BMI 430 kg m À2 ), is affecting both industrialized and many developing countries in the world, and constitutes a major public health problem. 4,6,7 In particular, in the United States, the prevalence of obesity was estimated at 32% of the population. Being overweight was even more prevalent, representing 42% of men and 28% of women, of whom 34 and 39%, respectively, had high blood pressure (BP). 8,9 The coexistence of hypertension and excessive BW greatly enhances cardiovascular risk. 2,10 Recent recommendations suggest the use of stratification tables to calculate the percentage of increased cardiovascular risk in patients with hypertension and excess BW or obesity. 11 The mechanisms underlying hypertension in subjects with excessive BW

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“…The activities of ALT (-16% in group O, -18% in group E, -14% on group OE, all P < 0.05) and gamma-glutamyl-transpeptidase (gGT, -15% in group O, -11% in group E, -25% in group OE, all P < 0.05) were improved in all treatment groups, whereas aspartate aminotransferase activity improved only in the combination group (-17%, P < 0.05). [16] ↓Visceral fat area ↓HOMA ↓Triglycerides, ↓total cholesterol, ↓LDL-C ↓ALT ↓hsCRP ↓Steatosis grade and NAFLD activity score Ezetimibe plus weight loss [17] ↓Intrahepatic triglyceride content ↓hsCRP ↓Interleukin-6 ↓LDL-C Ezetimibe plus orlistat [20][21][22] ↓Body mass index and waist circumference ↓Total cholesterol and triglycerides ↓HOMA ↓ALT, AST, γGT NAFLD: Non-alcoholic fatty liver disease; HOMA: Homeostasis model assessment; LDL-C: Low density lipoprotein cholesterol; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γGT: γ-glutamyltranspeptidase; hsCRP: High sensitivity C-reactive protein.…”

Section: Role Of Drug Combinations Including Ezetimibe In Nafldmentioning

confidence: 99%

“…Our group investigated the ezetimibe-orlistat combination treatment in 88 overweight and obese patients with hypercholesterolemia, who were randomised to ezetimibe (group E), orlistat (group O) and their combination (group OE) [20][21][22] . We observed significant within-group changes in body mass index, waist circumference and body weight, which were significantly greater in groups receiving orlistat.…”

Section: Role Of Drug Combinations Including Ezetimibe In Nafldmentioning

confidence: 99%

Role of ezetimibe in non-alcoholic fatty liver disease

Filippatos

Elisaf

2011

WJH

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Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis, advanced fibrosis and inflammatory changes. Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes. The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1). Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol. Ezetimibe exerts beneficial effects on several metabolic variables. Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers. The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients. Our group investigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholesterolemia, with beneficial effects on NAFLD biochemical markers. These results are promising for patients with NAFLD, who usually have increased cardiovascular disease risk and need a multifactorial treatment. However, it should be mentioned that most results are from animal studies and, although modest elevation of liver function tests may raise the suspicion of NAFLD, none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy

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The effect of orlistat and ezetimibe, alone or in combination, on serum LDL and small dense LDL cholesterol levels in overweight and obese patients with hypercholesterolaemia

Cited by 67 publications

References 52 publications

Ezetimibe Treatment Lowers Indicators of Oxidative Stress in Hypercholesterolemic Subjects with High Oxidative Stress

Ezetimibe Treatment Lowers Indicators of Oxidative Stress in Hypercholesterolemic Subjects with High Oxidative Stress

Effect of body weight loss and normalization on blood pressure in overweight non-obese patients with stage 1 hypertension

Role of ezetimibe in non-alcoholic fatty liver disease

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