Comparative effects of cholesteryl ester transfer protein inhibition, statin or ezetimibe on lipid factors: The ACCENTUATE trial.

BACKGROUND AND AIMS: The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters. METHODS: 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States. Lipid parameters, safety and tolerability were measured. RESULTS: Addition of evacetrapib significantly reduced LDL-C (-33%) compared with ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%, p<0.001). Evacetrapib also decreased apoB by 23% compared to 19% with ezetimibe (p=0.06) and 7% with increased statin dose (p<0.001), and reduced Lp(a) by 29% (p<0.001 vs. other groups). Evacetrapib increased HDL-C (+125%), apoA-I (+46%), apoC-III (+50%) and apoE (+28%) (p<0.001 vs. other groups). Non-ABCA1-mediated efflux increased by 53% (p<0.001 vs. other groups) with evacetrapib. ABCA1-mediated efflux also increased by 13% with evacetrapib (p<0.001 vs. ezetimibe, p=0.002 vs. increasing statin dose, and p=0.004 vs. statin alone). Addition of evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe (p=0.02). CONCLUSIONS: While evacetrapib improved traditional atherogenic and putative protective lipid measures compared with ezetimibe and increasing statin dose in patients with ASCVD and/or diabetes, it also adversely affected novel atherogenic risk factors. These findings may contribute to the lack of clinical benefit observed in the ACCELERATE trial.

Age effects on visual-perceptual processing and confrontation naming.

The impact of age-related changes in visual-perceptual processing on naming ability has not been reported. The present study investigated the effects of 6 levels of spatial frequency and 6 levels of contrast on accuracy and latency to name objects in 14 young and 13 older neurologically normal adults with intact lexical-semantic functioning. Spatial frequency and contrast manipulations were made independently. Consistent with the hypotheses, variations in these two visual parameters impact naming ability in young and older subjects differently. The results from the spatial frequency-manipulations revealed that, in general, young vs. older subjects are faster and more accurate to name. However, this age-related difference is dependent on the spatial frequency on the image; differences were only seen for images presented at low (e.g., 0.25-1 c/deg) or high (e.g., 8-16 c/deg) spatial frequencies. Contrary to predictions, the results from the contrast manipulations revealed that overall older vs. young adults are more accurate to name. Again, however, differences were only seen for images presented at the lower levels of contrast (i.e., 1.25%). Both age groups had shorter latencies on the second exposure of the contrast-manipulated images, but this possible advantage of exposure was not seen for spatial frequency. Category analyses conducted on the data from this study indicate that older vs. young adults exhibit a stronger nonliving-object advantage for naming spatial frequency-manipulated images. Moreover, the findings suggest that bottom-up visual-perceptual variables integrate with top-down category information in different ways. Potential implications on the aging and naming (and recognition) literature are discussed.