Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

Effect of five single nucleotide polymorphisms of ABCG5 and ABCG8 genes on eLipid-lowering response / Efecto de cinco polimorfismos de los genes ABCG5 y ABCG8 sobre la respuesta hipolipemiante a ezetimiba

In this study we evaluated the possible association between five single nucleotide polymorphisms in ABCG5 (rs6720173) and ABCG8 (rs11887534, rs4148211, rs4148217 and rs6544718) genes and ezetimibe response in Chilean hypercholesterolemic subjects. A total of 60 non-related hypercholesterolemic subjects, aged 18 to 65 years old were included in this study. These subjects were treated with ezetimibe (10mg/day) during one month. The ABCG5 and ABCG8 genotypes were assessed by PCR-RFLP. The genotype distribution of the ABCG5/ABCG8 polymorphisms was in Hardy-Weinberg equilibrium. Our results showed that the investigated polymorphisms were not associated with the response to ezetimibe. Nevertheless, the T allele of rs6544718 polymorphism was related to higher baseline levels of LDL-cholesterol (p<0.001). In addition, the G allele for the rs4148211 polymorphism was associated with greater baseline concentrations of triglycerides (P=0.019). This allele was also associated with lower concentrations of HDL-cholesterol (P=0.027), after ezetimibe treatment. Our results suggest that the studied polymorphisms do not affect the therapeutic response to ezetimibe in the evaluated subjects.

En este estudio se evaluó la posible asociación entre cinco polimorfismos de nucleótido único en los genes ABCG5 (rs6720173) y ABCG8 (rs11887534, rs4148211, rs4148217 y rs6544718) y la respuesta a ezetimiba en pacientes hipercolesterolémicos chilenos. Un total de 60 individuos hipercolesterolemicos, no relacionados, con edades entre 18 y 65 años fueron incluidos. Estos sujetos fueron tratados con ezetimiba (10mg/día) durante un mes. Los genotipos de ABCG5 y ABCG8 fueron evaluados por PCR-RFLP. La distribución de genotipos de los polimorfismos de ABCG5/ABCG8 se encontraba en equilibrio de Hardy-Weinberg. Nuestros resultados mostraron que los polimorfismos estudiados no se asociaron con la respuesta a la ezetimiba. Sin embargo, el alelo T del polimorfismo rs6544718 fue relacionado con niveles basales elevados de LDL-colesterol (p <0,001). Además, el alelo G para el polimorfismo rs4148211 se asoció con una mayor concentración basal de triglicéridos (p = 0,019). Este alelo también se asoció con concentraciones más bajas de HDL-colesterol (p = 0,027), después del tratamiento con ezetimiba. Nuestros resultados sugieren que los polimorfismos estudiados no afectan a la respuesta terapéutica a la ezetimiba en los sujetos evaluados.

Effect of atorvastatin, with or without ezetimibe, on serum lipid profile and ALT in hyperlipidemic patients

Hyperlipidaemia is raised serum levels of one or more of total cholesterol, low-density lipoprotein and triglycerides. Many drugs have been used for the treatment of this disorder. This work compares the effects of atorvastatin with or without ezetimibe on lipid profile, atherogenic index and serum alanine aminotransferase. This study covers 90 subjects, 60 untreated hyperlipidemic patients, and 30 healthy subjects. Patients were divided into 2 groups, the first group included 30 patients treated with atorvastatin 20 mg/day alone, the second group included 30 patients treated with a combination of 2 drugs [atorvastatin 10 mg plus ezetimibe 10 mg] taken daily at night. Serum lipid profile, atherogenic index and serum alanine amniotransferase were measured after 12 hours fasting for the patients in 3 intervals: before, and after 8 weeks and 16 weeks of treatment. After therapy for both groups of patients, as compared to the levels before treatment, has shown that serum total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol were significantly reduced while high density lipoprotein cholesterol was significantly increased. Serum alanine aminotransferase increased by both groups of treatment with no significant difference between the two modes of treatment which has the same findings in comparison to the control group. Combination of atorvastatin 10 mg and ezetimibe 10 mg daily, is more effective than atorvastatin 20 mg taken alone