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 .)

Dynamic Relation Between Working Memory Capacity and Speech Recognition in Noise During the First 6 Months of Hearing Aid Use

The present study aimed to investigate the changing relationship between aided speech recognition and cognitive function during the first 6 months of hearing aid use. Twenty-seven first-time hearing aid users with symmetrical mild to moderate sensorineural hearing loss were recruited. Aided speech recognition thresholds in noise were obtained in the hearing aid fitting session as well as at 3 and 6 months postfitting. Cognitive abilities were assessed using a reading span test, which is a measure of working memory capacity, and a cognitive test battery. Results showed a significant correlation between reading span and speech reception threshold during the hearing aid fitting session. This relation was significantly weakened over the first 6 months of hearing aid use. Multiple regression analysis showed that reading span was the main predictor of speech recognition thresholds in noise when hearing aids were first fitted, but that the pure-tone average hearing threshold was the main predictor 6 months later. One way of explaining the results is that working memory capacity plays a more important role in speech recognition in noise initially rather than after 6 months of use. We propose that new hearing aid users engage working memory capacity to recognize unfamiliar processed speech signals because the phonological form of these signals cannot be automatically matched to phonological representations in long-term memory. As familiarization proceeds, the mismatch effect is alleviated, and the engagement of working memory capacity is reduced