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 .)

Optical Limiting With Semiconductors

We present a detailed characterization of the output of passive semiconductor-based optical limiters. These devices utilize two-photon absorption along with photogenerated carrier defocusing within the material to limit the output fluence and irradiance. In addition to protecting downstream optical components, the focusing geometry combined with these nonlinearities makes the devices self-protecting. Such devices have a broad working wavelength range since both the initial two-photon absorption and the subsequent carrier refraction are slowly varying funtions of wavelength. For example, ZnSe should have a useful range of from 0.5 to 0.85 μm. In this material we have observed the onset of limiting at input powers as low as 80 W when using 10-nsec, 0.53 μm input pulses. At the same wavelength, when 30 psec pulses into a monolithic ZnSe limiter are used, limiting begins at ≃300 W or 10 nJ. We also monitored the output spatial energy distribution along with the temporal response at each position, using a 2-psec-resolution streak camera. We found that the output fluence along with the output irradiance is effectively limited below detector damage thresholds over an input range of 4 orders of magnitude. Additionally, since both two-photon absorption and the associated self-defocusing increase with decreasing band-gap energy, similar devices using narrow-gap semiconductors should have considerably lower limiting thresholds