Recent clinical trials and meta-analyses have indicated that high-intensive statin treatment lowers low-density lipoprotein cholesterol (LDL-C) levels and reduces the risk of nonfatal cardiovascular (CV) events compared with moderate-intensity statin treatment. However, there are residual risks of CV events and safety concerns associated with high-intensity statin treatment. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) study showed that ezetimibe plus moderate-intensity statin therapy after acute coronary syndromes incrementally lowers LDL-C levels and improved CV outcomes compared with moderate-intensity statin therapy. However, despite the LDL-C-lowering effects, a substantial residual CV risk still remains, which includes other lipid abnormalities such as low high-density lipoprotein cholesterol (HDL-C). The most representative agents that primarily increase HDL-C are cholesteryl ester transfer protein (CETP) inhibitors. Until now, 4 CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, and anacetrapib, have been introduced and all have significantly raised the HDL-C from 30% to 133%. However, the results for CV outcomes in clinical trials differed, based on the 4 agents. Torcetrapib increased the risk of CV events and total mortality in patients at high CV risk (ILLUMINATE trial). Dalcetrapib and evacetrapib did not result in lower rate of CV events in patients with recent acute coronary syndrome and high risk vascular disease, respectively (dal-OUTCOMES and ACCELERATE trials). However, anacetrapib significantly decreased the incidence of major coronary events in patients with atherosclerotic vascular disease (REVEAL trial). This topic summarizes the major results of recent statin and CETP inhibitor trials and provides framework to interpret and implement the trial results in real clinical practice.
Acute Coronary Syndrome ; Cholesterol ; Cholesterol Ester Transfer Proteins ; Dyslipidemias ; Ezetimibe ; Ezetimibe, Simvastatin Drug Combination ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Incidence ; Lipoproteins ; Mortality ; Vascular Diseases

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

No abstract available.
Humans ; Simvastatin* ; Ezetimibe

PURPOSE: The effects of short-term intensive lipid-lowering treatment on coronary plaque composition have not yet been sufficiently evaluated. We investigated the influence of short-term intensive lipid-lowering treatment on quantitative and qualitative changes in plaque components of non-culprit lesions in patients with acute coronary syndrome. MATERIALS AND METHODS: This was a prospective, randomized, open-label, single-center trial. Seventy patients who underwent both baseline and three-month follow-up virtual histology intravascular ultrasound were randomly assigned to either an intensive lipid-lowering treatment group (ezetimibe/simvastatin 10/40 mg, n=34) or a control statin treatment group (pravastatin 20 mg, n=36). Using virtual histology intravascular ultrasound, plaque was characterized as fibrous, fibro-fatty, dense calcium, or necrotic core. Changes in plaque components during the three-month lipid-lowering treatment were compared between the two groups. RESULTS: Compared with the control statin treatment group, there was a significant reduction in low-density lipoprotein cholesterol in the intensive lipid-lowering treatment group (-20.4±17.1 mg/dL vs. -36.8±17.4 mg/dL, respectively; p<0.001). There were no statistically significant differences in baseline, three-month follow-up, or serial changes of gray-scale intravascular ultrasound parameters between the two groups. The absolute volume of fibro-fatty plaque was significantly reduced in the intensive lipid-lowering treatment group compared with the control group (-1.5±3.4 mm3 vs. 0.8±4.7 mm3, respectively; p=0.024). A linear correlation was found between changes in low-density lipoprotein cholesterol levels and changes in the absolute volumes of fibro-fatty plaque (p<0.001, R2=0.209). CONCLUSION: Modification of coronary plaque may be attainable after only three months of intensive lipid-lowering treatment.
Aged ; Cholesterol, LDL/*blood/drug effects ; Coronary Artery Disease/*diagnostic imaging ; Drug Administration Schedule ; Ezetimibe, Simvastatin Drug Combination/*administration & dosage ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage ; Male ; Middle Aged ; Plaque, Atherosclerotic/*diagnostic imaging ; Pravastatin/administration & dosage ; Prospective Studies ; Time Factors ; Treatment Outcome ; Ultrasonography, Interventional

No abstract available.
Ezetimibe* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Mean Platelet Volume*

No abstract available.
Diabetes Mellitus, Type 2 ; Ezetimibe ; Humans ; Rosuvastatin Calcium

No abstract available.
Diabetes Mellitus, Type 2 ; Ezetimibe ; Humans ; Rosuvastatin Calcium

BACKGROUND AND OBJECTIVES: Ezetimibe alone does not decrease C-reactive protein (CRP) levels in hypercholesterolemic patients. However, several reports have suggested that ezetimibe might potentiate the effect of statin not only on cholesterol but also on CRP when administered together. We investigated the effect of ezetimibe on CRP levels in patients taking statins. SUBJECTS AND METHODS: Patients who had not achieved recommended low density lipoprotein-cholesterol (LDL-C) goals with statin therapy were divided into two groups, the ezetimibe group (n=60) and the control group (n=60). A third group of hypercholesterolemic patients without statin therapy was treated with statin (n=59). Patients with CRP level 10 mg/L were excluded. Lipid and CRP levels were measured before therapy commenced, and after 2 months of therapy. RESULTS: Ezetimibe decreased cholesterol and LDL-C levels by 20.2% (p=0.000) and 28.1% (p=0.000) respectively. However, ezetimibe did not reduce CRP levels (from 0.83+/-0.68 to 1.14+/-1.21 mg/dL, p=0.11). CRP levels remained unchanged in the control group (p=0.42). In contrast, statin lowered CRP levels (from 0.82+/-0.73 to 0.65+/-0.57 mg/dL, p=0.008). In patients taking statins, changes in CRP levels were not associated with changes in LDL-C (r=-0.02, p=0.87), but with baseline CRP levels (r=-0.38, p=0.000). CONCLUSION: Ezetimibe failed to reduce CRP levels in hypercholesterolemic patients taking statins despite significant reduction of LDL-C. This finding suggests that the anti-inflammatory effect of statin may not be secondary to cholesterol reduction, but via other mechanisms.
Azetidines ; C-Reactive Protein ; Cholesterol ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoproteins ; Ezetimibe

BACKGROUND AND OBJECTIVES: The inhibition of cholesterol absorption by ezetimibe increases cholesterol synthesis. The effect of inhibition of cholesterol synthesis on cholesterol absorption is controversial. The influence of these interactions on cholesterol levels is unknown. We investigated on the extent to which cholesterol levels were affected by the reaction of one pathway to the inhibition of the other pathway. SUBJECTS AND METHODS: This case-controlled study enrolled 198 patients who needed cholesterol-lowering drugs. Ezetimibe (10 mg) was administered to the patients with (n=58) and without on-going statin therapy (n=58). Simvastatin (20 mg) was administered to the patients treated with (n=41) and without ezetimibe (n=41). RESULTS: Ezetimibe without statin lowered the total cholesterol by 13.3+/-8.8% (p<0.001) and the low density lipoprotein-cholesterol (LDL-C) by 18.7+/-15.3% (p<0.001). Ezetimibe added to statin decreased the total cholesterol by 21.1+/-7.7% (p<0.001) and the LDL-C by 29.9+/-12.6% (p<0.001). The total cholesterol and LDL-C were reduced more by ezetimibe in patients with statin therapy than in those without statin therapy (p<0.001 and p<0.001, respectively). The differences in the effect of simvastatin on total cholesterol and LDL-C between the patients with and without ezetimibe showed borderline significance (p=0.10 and p=0.055, respectively). CONCLUSION: A prior inhibition of cholesterol synthesis by statin enhanced the effect of ezetimibe on total cholesterol and LDL-C by 7.8% and 11.2%, respectively. This finding suggests that ezetimibe increased cholesterol synthesis, resulting in a significant elevation of cholesterol levels.
Absorption ; Case-Control Studies ; Cholesterol ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Lipoproteins ; Simvastatin ; Ezetimibe

Latest guidelines on lipid management recommend statins as the first-line therapy. Because limited evidence is available on cardiovascular outcomes with varying statin-nonstatin combinations, recommendation levels for these regimens have been weak. However, a recent trial has demonstrated the additive effect of the statin-ezetimibe combination. The statin-fibrate combination has shown an effect in certain subgroups and on diabetic microangiopathy. Recent trials using the statin-niacin combination have been largely negative, whereas the statin-omega-3 fatty acids combination demonstrated a positive effect only in one study. Identifying the benefits and limitations of each combination is important for the best possible management of patients.
Diabetic Angiopathies ; Drug Therapy* ; Ezetimibe ; Fatty Acids ; Fibric Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Niacin