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 .)

Upper-mesospheric temperatures measured during intense substorms in the declining phase of the January 2005 solar proton events

Temperature measurements from the ALOMAR Weber Na lidar together with cosmic radio noise absorption measurements from IRIS and particle measurements from NOAA 15, 16 and 17 are used to study effects of geomagnetic activity on the polar winter upper-mesospheric temperature. On 21–22 January 2005 we have 14 h of continuous temperature measurement with the Na lidar coinciding with strong geomagnetic activity in the declining phase of one of the hardest and most energetic Solar Proton Event (SPE) of solar cycle 23. According to measurements by the imaging riometer IRIS in northern Finland, the temperature measurements coincide with two periods of increased cosmic radio noise absorption. Particle measurements from the three satellites, NOAA 15, 16 and 17 that pass through and near our region of interest confirm that the absorption events are probably due to particle precipitation and not due to changes in e.g. the electron recombination coefficient. <br><br> The measured temperature variation at 85 and 90 km is dominated by a 7.6-h wave with downward phase propagation and a vertical wavelength of approximately 10 km. Assuming that the wave is due to a lower altitude source independent of the particle precipitation, we do not find any temperature modification that seems to be related to the absorption events. The average temperature is larger than expected above 90 km based on MSIS and the monthly mean from falling spheres, which could be due to particle precipitation and Joule heating prior to our measurement period. There is also a possibility that the identified wave phenomenon is an effect of the geomagnetic activity itself. Earlier studies have reported of similar wavelike structures in wind observations made by the EISCAT VHF radar during SPEs, and found it conceivable that the wave could be excited by the effect of energetic particles precipitating into the mesosphere

Pi2-pulsations observed in energetic electron precipitation and magnetic field in association with a substorm surge

For a substorm 24 July 1998 PIXIE observes the onset and expansion during a perigee pass of the Polar satellite. This gives an opportunity to follow the evolution of the onset and expansion phase, almost on a global scale with relatively high temporal resolution. The substorm is presented with multiple observations throughout the magnetosphere. Following the onset of the substorm we observe a localised region of modulated energetic electron fluxes following the passage of the westward travelling surge in the pre-midnight region. We count at least six clear pulses with a period of approximately one minute. Concurrent magnetic ground measurements show similar characteristics, almost simultaneously with the pulses in precipitation. We propose several possible mechanism for the pulsations, amongst them the theory of modulated wave particle interaction first proposed by coroniti70