ezetimibe--simvastatin-drug-combination and Atherosclerosis

The effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial. We thus determined the concentration of atherogenic small, dense LDL (sdLDL) in patients with type 2 diabetes and an elevated cardiovascular risk profile.. Multicenter, randomized, open-label 6-week study investigating the effect of ezetimibe 10mg (E), simvastatin 20mg (S) and the combination of ezetimibe-/simvastatin 10/20mg (C) on the concentration of sdLDL separated from fresh plasma by gradient ultracentrifugation in patients with type 2 diabetes (NCT01384058).. Fifty-six patients were screened for sdLDL, 41 were randomized, and 40 patients (12 E, 14 S and 14 C) completed the study. Total and LDL cholesterol fell by 14% (p=0.004) and 15% (p=0.006) with E, 22% (p<0.001) and 32% (p<0.001) with S, and 32% (p<0.001) and 44% (p<0.001) with C, respectively. E reduced the concentration of sdLDL by 20% (p=0.043) whereas S and C reduced sdLDL by 24% (p=0.020) and 33% (p=0.003), respectively, and non-sdLDL by 28% (p=0.004) and 42% (p<0.001), respectively. However, the further drop in sdLDL by adding E to S was not significant.. Ezetimibe alone and in combination with simvastatin reduced the concentration of atherogenic sdLDL in patients with type 2 diabetes.

Topics: Aged; Analysis of Variance; Anticholesteremic Agents; Atherosclerosis; Azetidines; Biomarkers; Centrifugation, Density Gradient; Diabetes Mellitus, Type 2; Down-Regulation; Drug Combinations; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Female; Germany; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Linear Models; Lipoproteins, LDL; Male; Middle Aged; Risk Assessment; Risk Factors; Simvastatin; Time Factors; Treatment Outcome

This study sought to assess the impact of valvuloarterial impedance on left ventricular (LV) myocardial systolic function in asymptomatic aortic valve stenosis (AS).. In atherosclerotic AS, LV global load consists of combined valvular and arterial resistance to LV ejection. Global load significantly impacts LV ejection fraction (EF) in symptomatic AS, but less is known about its effect on LV myocardial function in asymptomatic AS.. Echocardiograms in 1,591 patients with asymptomatic AS (67 +/- 10 years, 51% hypertensive) at baseline in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) study evaluating placebo-controlled combined simvastatin and ezetimibe treatment in AS were used to assess LV global load as valvuloarterial impedance and LV myocardial function as stress-corrected midwall shortening. The study population was divided into tertiles of global load. Stress-corrected midwall shortening was considered low if <87% in men and <90% in women. Low-flow AS was defined as stroke volume index <22 ml/m(2.04).. Energy loss index decreased (0.85 cm(2)/m(2) vs. 0.77 and 0.75 cm(2)/m(2)) and the prevalence of low stress-corrected midwall shortening increased (10% vs. 26% and 63%) with increasing LV global load (all p < 0.001). The EF was low in only 2% of patients. Patients with low-flow AS had higher LV global load and more often low midwall shortening than those with normal-flow AS (9.66 +/- 2.23 mm Hg/ml.m(2.04) and 77%, vs. 6.38 +/- 2.04 mm Hg/ml.m(2.04) and 30%, respectively, p < 0.001). In logistic regression analysis, LV global load was a main predictor of low stress-corrected midwall shortening independent of male sex, concentric LV geometry, LV hypertrophy (all p < 0.001), concomitant hypertension, and aortic regurgitation.. LV global load impacts LV myocardial function in asymptomatic AS independent of other main covariates of LV systolic function. LV myocardial systolic dysfunction is common in asymptomatic AS in particular in patients with low-flow AS and increased valvuloarterial afterload, whereas EF is generally preserved. (An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis [Narrowing of the Major Blood Vessel of the Heart]; NCT00092677).

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Atherosclerosis; Azetidines; Disease Progression; Double-Blind Method; Drug Combinations; Echocardiography, Doppler; Europe; Ezetimibe, Simvastatin Drug Combination; Female; Hemodynamics; Humans; Hypolipidemic Agents; Logistic Models; Male; Middle Aged; Myocardial Contraction; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Sensitivity and Specificity; Simvastatin; Systole; Treatment Outcome; United States; Ventricular Dysfunction, Left

Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95-1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35-0.72), PCI (SHR, 0.82; 95% CI, 0.69-0.97) and CABG (SHR, 0.62; 95% CI, 0.40-0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Atherosclerosis; Diabetes Mellitus, Type 2; Disease Management; Disease Susceptibility; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Risk Factors; Treatment Outcome

Topics: Atherosclerosis; Azetidines; Clinical Trials as Topic; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Hypolipidemic Agents; Kidney Failure, Chronic; Learning; Simvastatin

Topics: Anticholesteremic Agents; Atherosclerosis; Azetidines; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Simvastatin

Topics: Aortic Valve Stenosis; Atherosclerosis; Azetidines; Calcinosis; Disease Progression; Drug Combinations; Echocardiography, Doppler; Ezetimibe, Simvastatin Drug Combination; Hemodynamics; Humans; Hypolipidemic Agents; Myocardial Contraction; Predictive Value of Tests; Risk Assessment; Risk Factors; Simvastatin; Systole; Treatment Outcome; Ventricular Dysfunction, Left