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 .)

Recent research on Arctic benthos: common notions need to be revised

Increased public awareness of the global significance of polar regions and opening of the Russian Arctic to foreign researchers have led to a pronounced intensification of benthic research in Arctic seas. The wealth of information gathered in these efforts has markedly enhanced our knowledge on the Arctic benthos. While some scientific concepts have been corroborated by the novel findings (e.g., low endemism and high faunistic affinity to northern Atlantic assemblages), other common notions need to be revised, particularly with regard to the often-cited differences between Arctic seas and the Southern Ocean. It has been demonstrated that benthos assemblages vary broadly in diversity between Arctic regions and that, hence, the idea of a consistently poor Arctic benthos—being in stark contrast to the rich Antarctic bottom fauna—is an undue overgeneralization. In terms of biogeographic diversity, both Arctic and Antarctic waters seem to be characterized by intermediate species richness. Levels of disturbance—a major ecological agent known to heavily affect benthic diversity and community structure—have been assumed to be relatively high in the Arctic but exceptionally low in the Southern Ocean. The discovery of the great role of iceberg scouring in Antarctic shelf ecosystems, which has largely been overlooked in the past, calls for a reconsideration of this notion. The novel data clearly demonstrate that there are marked differences in geographical and environmental setting, impact of fluvial run-off, pelagic production regime, strength of pelago–benthic coupling and, hence, food supply to the benthos among the various Arctic seas, impeding the large-scale generalization of local and regional findings. Field evidence points to the great significance of meso-scale features in hydrography and ice cover (marginal ice zones, polynyas, and gyres) as ‘hot spots’ of tight pelago–benthic coupling and, hence, high benthic biomass. In contrast, the importance of terrigenic organic matter discharged to the Arctic seas through fluvial run-off as an additional food source for the benthos is still under debate. Studies on the partitioning of energy flow through benthic communities strongly suggest that megafauna has to be adequately considered in overall benthic energy budgets and models of carbon cycling, particularly in Arctic shelf systems dominated by abundant echinoderm populations. Much progress has been made in the scientific exploration of the deep ice-covered Arctic Ocean. There is now evidence that it is one order of magnitude more productive than previously thought. Therefore, the significance of shelf–basin interactions, i.e., the importance of excess organic carbon exported from productive shelves to the deep ocean, is still debated and, hence, a major topic of on-going research. Another high-priority theme of current/future projects are the ecological consequences of the rapid warming in the Arctic. Higher water temperatures, increased fluvial run-off and reduced ice cover will give rise to severe ecosystem changes, propagating through all trophic levels. It is hypothesized that there would be a shift in the relative importance of marine biota in the overall carbon and energy flux, ultimately resulting in a switch from a ‘sea-ice algae–benthos’ to a ‘phytoplankton–zooplankton’ dominance