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 .)

A breccia-centered ore and alteration model for the Copper Canyon alkalic Cu-Au porphyry deposit, British Columbia

Thesis (M.S.) University of Alaska Fairbanks, 2007Similar to the nearby Galore Creek deposit, the Copper Canyon prospect of northwestern British Columbia is a porphyry-type copper-gold-silver occurrence associated with alkalic intrusive rocks of the Late Triassic-Early Jurassic Copper Mountain Suite. A reevaluation of the prospect geology shows that, of the previously recognized orthoclase and/or pseudoleucite porphyry syenite intrusions, mineralization is spatially and temporally associated with a single intrusive phase (unit i5) and biotite-garnet stockworks. Further, a newly defined unit of pre-mineralization magmatic-hydrothermal intrusive breccia occupies the core of the prospect and is a favorable host for much of the prospect mineralization. Prospect alteration can be divided into two distinct styles. Calc-potassic alteration consists of K-feldspar, Mg and Fe³-rich (An₂₀) biotite, andradite-rich garnet, hematite, magnetite, chalcopyrite, pyrite, and sphalerite (Zn₉₄₋₉₉, Fe₀.₅₋₂, Cd₀.₄₋₁)S and is associated with copper-gold-silver mineralization. Ankerite-sericite-pyrite (± fluorite, albite, anhydrite, pyrite, and trace covellite and bornite) alteration adjoins this core, hosting gold mineralization and insignificant copper. Sulfide-electrum and biotite geothermometry suggest fluid temperatures decreasing from the core (<̲S 550°C) to distal gold mineralization (<̲361°C). Distal gold mineralization is most likely the result of higher than typical sulfur activity and bisulfide transport of gold

Oligocene-Neogene lithospheric-scale reactivation of Mesozoic terrane accretionary structures in the Alaska Range suture zone, southern Alaska, USA

Terrane accretion forms lithospheric-scale fault systems that commonly experience long and complex slip histories. Unraveling the evolution of these suture zone fault systems yields valuable information regarding the relative importance of various upper crustal structures and their linkage through the lithosphere. We present new bedrock geologic mapping and geochronology data documenting the geologic evolution of reactivated shortening structures and adjacent metamorphic rocks in the Alaska Range suture zone at the inboard margin of the Wrangellia composite terrane in the eastern Alaska Range, Alaska, USA. Detrital zircon uranium-lead (U-Pb) age spectra from metamorphic rocks in our study area reveal two distinct metasedimentary belts. The Maclaren schist occupies the inboard (northern) belt, which was derived from terranes along the western margin of North America during the mid- to Late Cretaceous. In contrast, the Clearwater metasediments occupy the outboard (southern) belt, which was derived from arcs built on the Wrangellia composite terrane during the Late Jurassic to Early Cretaceous. A newly discovered locality of Alaska-type zoned ultramafic bodies within the Clearwater metasediments provides an additional link to the Wrangellia composite terrane. The Maclaren and Clearwater metasedimentary belts are presently juxtaposed by the newly identified Valdez Creek fault, which is an upper crustal reactivation of the Valdez Creek shear zone, the Late Cretaceous plate boundary that initially brought them together. / Ar mica ages reveal independent post-collisional thermal histories of hanging wall and footwall rocks until reactivation localized on the Valdez Creek fault after ca. 32 Ma. Slip on the Valdez Creek fault expanded into a thrust system that progressed southward to the Broxson Gulch fault at the southern margin of the suture zone and eventually into the Wrangellia terrane. Detrital zircon U-Pb age spectra and clast assemblages from fault-bounded Cenozoic gravel deposits indicate that the thrust system was active during the Oligocene and into the Pliocene, likely as a far-field result of ongoing flat-slab subduction and accretion of the Yakutat microplate. The Valdez Creek fault was the primary reactivated structure in the suture zone, likely due to its linkage with the reactivated boundary zone between the Wrangellia composite terrane and North America in the lithospheric mantle.This work was funded by grants from the American Association of Petroleum Geologists, Alaska Geological Society, Geological Society of America, and UC Davis Durrell Fund (T.S. Waldien), U.S. Geological Survey National Cooperative Geologic Mapping Program award #G16AC00206 (S.M. Roeske and T.S. Waldien), National Science Foundation (NSF) Tectonics award #EAR-1828737 to S.M. Roeske and #EAR-1828023 to J.A. Benowitz, and the State of Alaska Strategic and Critical Minerals Assessment program (E. Twelker)