ezetimibe--simvastatin-drug-combination and Carotid-Artery-Diseases

Patients with heterozygous familial hypercholesterolemia (FH) have an increased risk of premature myocardial infarction, stroke, and surgical revascularization, and an increased rate of progression of carotid intima-media thickness (IMT). The most commonly used drugs for cholesterol lowering, statins, have a limited action in these patients. Ezetimibe, a novel compound, selectively inhibits cholesterol uptake and when associated with statins has an additional low-density lipoprotein cholesterol (LDL-C) reducing effect. The aim of this study is to evaluate the effects of long-term combined Ezetimibe/Simvastatin (EZE/SIMVA) therapy (30 months) on the lipidic pattern, inflammatory markers, and carotid IMT in patients with FH subdivided into two groups: one with a history of acute myocardial infarction (IMA) and the other with carotid atherosclerotic plaques but no history of cardiovascular events.. All patients enrolled in this study (group A: patients with a history of IMA; group B, patients with carotid lesions but no history of cardiovascular events) were submitted to a 6-week period of isocaloric diet and to a 4-week lipid-lowering wash-out period before study entry. After the wash-out period at baseline (time 0) and then every two months total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B and A1 were determined. LDL-C levels were calculated. Fibrinogen and hs-CRP at baseline and at 6, 18, and 30 months were determined. All patients were submitted to an ultrasonographic evaluation of the carotid intima-media thickness at baseline, 18 and 30 months. The scheduled duration time of the study was 30 months. At the beginning of the study all patients were assigned to receive the combined EZE/SIMVA treatment 10/20 mg per day. After two months, patients who had not reached the respective LDL-C targets proposed by NCEP ATPIII (<70 mg/dL for patients with a history of IMA and <100 mg/dL for patients with carotid lesions) were assigned to receive EZE/SIMVA 10/40 mg per day and, after four months, patients who had not reached the respective LDL-C targets were assigned to receive EZE/SIMVA 10/80 mg per day.. At the end-point, significant reductions (P<0.001) of about 70% in LDL-C, of 57% in total cholesterol (TC), of 46% in Apo-B, and of 46% in hs-C-reactive protein (hs-CRP) were observed in both groups compared to baseline. Also, triglyceride and fibrinogen levels were significantly (P<0.01) reduced, respectively by 26% and 15% compared to baseline. The EZE/SIMVA association resulted in significant increases in HDL-C (P<0.01) of 11% and in Apo-A1 (P<0.05) by 9% and in significant (P<0.001) reductions of the mean of the carotid IMT in both groups. The EZE/SIMVA treatment was generally well-tolerated, with a safety profile on laboratory parameters. During the 30-month scheduled period of the study, no patient in either group presented any further cardiovascular events.. In patients with FH, combined EZE/SIMVA treatment resulted in a significant LDL-C lowering, achieving the goals proposed by NCEP ATP III, in a significant improvement of all the lipidic and inflammatory patterns, and above all in a progressive decrease of the carotid IMT. Although the results of ongoing randomized controlled trials are required before making any definitive conclusions, our results support the hypothesis of stabilizing effect of EZE/SIMVA on the atherosclerotic disease both in primary and in secondary prevention.

Topics: Aged; Analysis of Variance; Anticholesteremic Agents; Apolipoprotein A-I; Apolipoproteins B; Azetidines; Biomarkers; C-Reactive Protein; Carotid Artery Diseases; Cholesterol; Cholesterol, HDL; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Female; Fibrinogen; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Inflammation Mediators; Italy; Male; Middle Aged; Myocardial Infarction; Primary Prevention; Secondary Prevention; Simvastatin; Time Factors; Treatment Outcome; Triglycerides; Ultrasonography

It remains uncertain whether statin/ezetimibe combination therapy serves as a useful and equivalent alternative to statin monotherapy for reducing atherosclerotic plaque inflammation. The aim of the present study was to compare the effects of statin/ezetimibe combination therapy and statin monotherapy on carotid atherosclerotic plaque inflammation using 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) imaging. Data were pooled from 2 clinical trials that used serial 18FDG PET/CT examination to investigate the effects of cholesterol-lowering therapy on carotid atherosclerotic plaque inflammation. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS) at 6-month follow-up. Baseline characteristics were largely similar between the 2 groups. At the 6-month follow-up, the MDS TBR of the index vessel significantly decreased in both groups. The percent change in the MDS TBR of the index vessel (primary outcome) did not differ significantly between the 2 groups (-8.41 ± 15.9% vs -8.08 ± 17.0%, respectively, P = .936). Likewise, the percent change in the whole vessel TBR of the index vessel did not differ significantly between the 2 groups. There were significant decreases in total and LDL cholesterol levels in both groups at follow-up (P < .001). There were no significant correlations between the percent changes in MDS TBR of the index vessel, changes in the lipid, and high-sensitive C-reactive protein levels. The reduction in carotid atherosclerotic plaque inflammation by statin/ezetimibe combination therapy was equivalent to that by the statin monotherapy.

Topics: Acute Coronary Syndrome; Aged; C-Reactive Protein; Carotid Arteries; Carotid Artery Diseases; Cholesterol, LDL; Clinical Trials as Topic; Datasets as Topic; Ezetimibe, Simvastatin Drug Combination; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Plaque, Atherosclerotic; Rosuvastatin Calcium; Simvastatin

Topics: Anticholesteremic Agents; Azetidines; Biomarkers; C-Reactive Protein; Carotid Artery Diseases; Cholesterol, LDL; Creatinine; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Simvastatin; Time Factors; Treatment Outcome; Triglycerides

Topics: Anticholesteremic Agents; Azetidines; Cardiovascular Diseases; Carotid Artery Diseases; Cholesterol, LDL; Drug Combinations; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Randomized Controlled Trials as Topic; Simvastatin; Treatment Outcome