No abstract

NCT01176968.

SUMMARYBackground: Pleiotropic effects of ezetimibe have only been investigated in a few studies. The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low-grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia. Methods: The study included 69 patients with elevated cholesterol levels, who were allocated to one of the three groups treated for 12 weeks, respectively, with simvastatin (40 mg daily), simvastatin (40 mg daily) plus ezetimibe (10 mg daily), or placebo. Plasma levels of lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin, tumor necrosis factor-a (TNF-a), free fatty acids (FFA), and high-sensitive C-reactive protein (hsCRP) were determined on the allocation day and after 12 weeks of therapy. Results: Apart from improving lipid profile, simvastatin administered alone or in combination with ezetimibe, decreased plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-a, as well as increased plasma levels of adiponectin. The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins, hsCRP, FFA, and the investigated adipokines. The effect of the combination therapy, but not of simvastatin, on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects. Conclusions: The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe.

Abstract. Krysiak R, Zmuda W, Okopien B (Medical University of Silesia, Katowice; and and Electrotherapy and Angiology Centre, Oswiecim, Poland). The effect of ezetimibe, administered alone or in combination with simvastatin, on lymphocyte cytokine release in patients with elevated cholesterol levels. J Intern Med 2012; 271: 32-42.Objective. Studies assessing the extra-lipid effects of ezetimibe have provided contrasting results. In the present study, we compared the effects of ezetimibe and simvastatin, administered alone or in combination, on the secretory function of human lymphocytes, systemic inflammation and endothelial function in subjects with elevated cholesterol levels. Methods.A prospective study involving a group of 178 ambulatory patients with isolated hypercholesterolaemia who were randomly assigned in a double-blind fashion to 90 days of treatment with ezetimibe (10 mg), simvastatin (40 mg), ezetimibe (10 mg) plus simvastatin (40 mg) or placebo. A total of 170 patients completed the study.Main outcome measures. Lymphocyte cytokine release and plasma levels of high-sensitivity C-reactive protein (hsCRP) and intercellular adhesion molecule 1 (ICAM-1).Results. Although both drugs reduced lymphocyte release of tumour necrosis factor-a, interferon-c and interleukin-2 in a lipid-independent manner, only the effect of simvastatin was statistically significant (P < 0.001). This lymphocyte-suppressing effect, which was accompanied by a decrease in plasma levels of hsCRP and ICAM-1 (P < 0.001), was strongest in patients receiving both simvastatin and ezetimibe. There were no differences in lymphocyte-suppressing, systemic anti-inflammatory and endothelial protective effects of simvastatin between insulinresistant and insulin-sensitive subjects, whereas the effects of ezetimibe and the combined treatment were greater in the former group of patients (P < 0.01 and P < 0.001, respectively).Conclusions. The results of this study indicate that simvastatin is superior to ezetimibe in producing lymphocyte-suppressing, systemic anti-inflammatory and endothelial protective effects in patients with elevated cholesterol levels. Hypercholesterolaemic patients with high cardiovascular risk may receive the greatest benefits from concomitant treatment with a statin and ezetimibe.

Aims  The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI). Methods and results  Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset &lt;24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0–100%), fibrinolysis (18.8%; 0–100%), and no reperfusion therapy (9.0%; 0–75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5–5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8–97.5%) for the performance of reperfusion therapy of all patients with STEMI &lt;12 h and 54.4% (region range 37.1–70.1%) for timely reperfusion. Conclusions  The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.