Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Experiments on the hydrodynamics of helium II.

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Association modèles et Systèmes d'Informations Géographiques pour l'évaluation du risque environnemental

Many types of models have been developed to predict the environmental fate of pesticides. However few have been developed specifically to work at the catchment level. At this scale, the requirement to link models with comprehensive spatial datasets describing important environmental variables is best achieved within the framework of a Geographic Information System. The use of models to evaluate environmental risks is discussed and some methods of linking databases, models, risk evaluations and GIS are described. Two GIS-based systems developed for evaluating the environmental risks to water resources from pesticide usage in the UK, are used as illustration. It is concluded that, at the catchment scale, the value of model-based risk evaluations depends both on the sophistication of the model used and the accuracy of the spatial environmental data it accesses. / Plusieurs types de modèles ont été développés pour prévoir le devenir des pesticides dans l'environnement. Au niveau du bassin hydrographique, la liaison des modèles à l'ensemble des bases de données spatiales qui décrivent les variables environnementales importantes est réalisée au mieux au sein d'un système d'informatique géographique (SIG). L'emploi de modèles pour l'évaluation des risques environnementaux est discuté, et plusieurs méthodes d'association bases de données, modèles, évaluations de risques et SIG sont décrites. En illustration, deux systèmes basés sur un SIG, développés au Royaume-Uni, sont présentés. Une des conclusions importantes est qu'à l'échelle du bassin hydrographique, les résultats de l'évaluation de risques basée sur les modèles dépendent à la fois de la sophistication de ces modèles et de la précision des données spatiales environnementales dont ils se servent