BACKGROUNDStatins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease.

METHODSForty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography.

RESULTSAfter treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P < 0.05). On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P < 0.001) compared to levels during the 4th week. By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P < 0.05) compared with levels measured during the 4th week.

CONCLUSIONSCoronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

Adult ; Aged ; Azetidines ; administration & dosage ; Cholesterol ; metabolism ; Cholesterol, LDL ; blood ; Coronary Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Humans ; Male ; Middle Aged ; Simvastatin ; administration & dosage

BACKGROUND/AIMS: The efficacy and safety of a combination of ezetimibe and low-dose statin as primary treatment for dyslipidemia in renal transplant patients were evaluated prospectively. METHODS: The study enrolled 77 renal transplant recipients with dyslipidemia. They were given ezetimibe (10 mg) and simvastatin (10 mg) for 6 months as the initial treatment for dyslipidemia. Efficacy and safety were evaluated using lipid profiles, trough calcineurin inhibitor levels, allograft function, and adverse effects. The effects on proteinuria and high sensitivity C-reactive protein (hsCRP) levels were also evaluated. RESULTS: Ezetimibe and low-dose simvastatin significantly decreased the levels of total cholesterol (34.6%), triglyceride (16.0%), and low-density lipoprotein cholesterol (LDL-C) (47.6%), and 82.5% of the patients reached the target LDL-C level of <100 mg/dL. No significant change in the trough calcineurin inhibitor levels or allograft function occurred, and no serious adverse effects were observed. Fourteen patients (18.2%) discontinued treatment; eight patients (11.7%) developed muscle pain or weakness without an increase in creatinine kinase levels, and two patients (2.6%) developed elevated liver transaminase levels. The proteinuria and hsCRP levels did not change significantly. CONCLUSIONS: Ezetimibe and low-dose statin treatment is safe and effective as a primary treatment for dyslipidemia in renal transplant patients.
Adult ; Azetidines/*administration & dosage/adverse effects ; C-Reactive Protein/analysis ; Cholesterol, LDL/blood ; Dyslipidemias/blood/*drug therapy ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage ; *Kidney Transplantation ; Male ; Middle Aged ; Prospective Studies ; Simvastatin/*administration & dosage/adverse effects

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337+/-227 vs. 443+/-366 cells, P=0.292), but neointima area was significantly smaller (1.00+/-0.49 mm2 vs. 1.69+/-0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3+/-10% vs. 39+/-19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99+/-0.79 vs. 1.81+/-0.88, P=0.49), endothelial score (1.75+/-0.66 vs. 1.80+/-0.59, P=0.79), and the percent of endothelium covered lumen (43+/-21% vs. 45+/-21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.
Animals ; Anticholesteremic Agents/administration & dosage ; Azetidines/*administration & dosage ; Coronary Restenosis/diagnosis/drug therapy/*etiology ; *Disease Models, Animal ; Drug Combinations ; Drug Implants/administration & dosage ; Drug-Eluting Stents/*adverse effects ; Female ; Graft Occlusion, Vascular/diagnosis/*drug therapy/*etiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Simvastatin/*administration & dosage ; Swine ; Treatment Outcome

INTRODUCTIONWe aimed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia.

METHODSA double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile, oxidised low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hsCRP) and soluble intercellular cell adhesion molecule (sICAM) in dyslipidaemic patients with or at high risk of coronary artery disease, and compare it with atorvastatin 10 mg monotherapy. 30 patients were randomised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks.

RESULTSOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference -14.4 ± 6.5, 95% confidence interval [CI] -1.0 to -27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference -19.9 ± 6.1, 95% CI -7.4 to -32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.

CONCLUSIONCombination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy.

Anti-Inflammatory Agents ; therapeutic use ; Anticholesteremic Agents ; administration & dosage ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Drug Therapy, Combination ; methods ; Dyslipidemias ; drug therapy ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; Humans ; Hypolipidemic Agents ; therapeutic use ; India ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipoproteins, LDL ; metabolism ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; Treatment Outcome

OBJECTIVEPatients with coronary artery disease (CAD, stenosis between 50% - 70% evidenced by coronary angiography) were treated with atorvastatin 40 mg (n = 19) or atorvastatin 10 mg in combination with ezetimibe 10 mg (n = 23). Blood lipid profile and metalloproteinases were monitored up to 3 months.

METHODSCholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), liver function, renal function, creatine kinase, MMP-2, MMP-9, TIMP-1 were measured at baseline and at 1 month and 3 months post therapy.

RESULTS(1) At 3 months, LDL-C was similarly reduced in monotherapy group [(1.94 +/- 0.49) mmol/L, 37.82% reduction compared to baseline] and in combined therapy group [(1.92 +/- 0.54) mmol/L, 38.26% reduction compared to baseline]. (2) AST, ALT, renal function and creatine kinase remained unchanged post various therapy (all P > 0.05). (3) MMP-2, MMP-9 significantly decreased and TIMP-1 significantly increased at 3 months compared to baseline in monotherapy group but these parameters remained unchanged in combined therapy group.

CONCLUSIONBoth therapy regimens were well tolerated and similarly effectively reduced blood lipids and 40 mg atorvastatin monotherapy regimen is superior to atorvastatin 10 mg plus ezetimibe 10 mg regimen in improving metalloproteinases parameters.

Adolescent ; Adult ; Aged ; Anticholesteremic Agents ; administration & dosage ; therapeutic use ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; therapeutic use ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Artery Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Hypolipidemic Agents ; administration & dosage ; therapeutic use ; Male ; Metalloproteases ; blood ; Middle Aged ; Pyrroles ; administration & dosage ; therapeutic use ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Treatment Outcome ; Young Adult