No abstract available.
Humans ; Simvastatin* ; Ezetimibe

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

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

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

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

BACKGROUND: Simvastatin belongs to the statin family, whose members have immunomodulatory activities. Ezetimibe have synergetic effects when co-administered with simvastatin. In several case reports, alopecia totalis and alopecia universalis were successfully treated with simvastatin/ezetimibe, suggesting that this combination could be a new efficient therapy for recalcitrant alopecia areata (AA). OBJECTIVE: To verify the efficacy of the simvastatin/ezetimibe combination therapy for recalcitrant AA and investigate the relationship between various treatment responses and prognostic factors. METHODS: This prospective open study was performed in patients with recalcitrant AA with the bald surface exceeding 75%. All patients took simvastatin (40 mg) and ezetimibe (10 mg) daily. The extent of hair regrowth expressed as percentage of the bald area was used to evaluate the effectiveness of the therapy. RESULTS: Of 14 enrolled patients, 4 patients (28.6%) were judged as responders showing regrowth of 30% to 80% after 3 months of treatment. The mean age of onset in non-responders was significantly lower than in responders. The total score of prognostic factors, calculated as a sum of factors related to poor prognosis, was much lower in responders than in non-responders. CONCLUSION: The remission rate in this study was unsatisfactory. However, since the recruited patients had not responded to any other treatments for AA, simvastatin/ezetimibe can still be considered as an alternative treatment for recalcitrant AA. The total scores of the prognostic factors were statistically different between responders and non-responders. These results can be used to predict the outcome of treatment with simvastatin/ezetimibe and anticipate prognosis.
Age of Onset ; Alopecia Areata* ; Alopecia* ; Ezetimibe ; Hair ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Prognosis ; Prospective Studies* ; Simvastatin

Atorvastatin and ezetimibe are frequently co-administered to treat patients with dyslipidemia for the purpose of low-density lipoprotein cholesterol control. However, pharmacokinetic (PK) drug interaction between atorvastatin and ezetimibe has not been evaluated in Korean population. The aim of this study was to investigate PK drug interaction between two drugs in healthy Korean volunteers. An open-label, randomized, multiple-dose, three-treatment, three-period, Williams design crossover study was conducted in 36 healthy male subjects. During each period, the subjects received one of the following three treatments for seven days: atorvastatin 40 mg, ezetimibe 10 mg, or a combination of both. Blood samples were collected up to 96 h after dosing, and PK parameters of atorvastatin, 2-hydroxyatorvastatin, total ezetimibe (free ezetimibe + ezetimibe-glucuronide), and free ezetimibe were estimated by non-compartmental analysis in 32 subjects who completed the study. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) of the maximum plasma concentration (C(max,ss)) and the area under the curve within a dosing interval at steady state (AUC(τ,ss)) of atorvastatin when administered with and without ezetimibe were 1.1087 (0.9799–1.2544) and 1.1154 (1.0079–1.2344), respectively. The corresponding values for total ezetimibe were 1.0005 (0.9227–1.0849) and 1.0176 (0.9465–1.0941). There was no clinically significant change in safety assessment related to either atorvastatin or ezetimibe. Co-administration of atorvastatin and ezetimibe showed similar PK and safety profile compared with each drug alone. The PK interaction between two drugs was not clinically significant in healthy Korean volunteers.
Atorvastatin Calcium* ; Cholesterol ; Cross-Over Studies ; Drug Interactions* ; Dyslipidemias ; Ezetimibe* ; Humans ; Lipoproteins ; Male ; Pharmacokinetics ; Plasma ; Volunteers*