3 research outputs found

    Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

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    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 .)

    Energy expenditure in the critically ill performing early physical therapy

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    Purpose: Resting energy expenditure (REE) determination is of high relevance to avoid both overfeeding and underfeeding. We conducted an observational study to determine the impact of early exercise on energy requirements to adjust caloric intake accordingly in critically ill patients. Methods: This was a prospective observational study conducted in an intensive care unit in 49 hemodynamically stable critically ill patients and 15 healthy volunteers. Indirect calorimetry (IC) was performed for 15 min at baseline during resting conditions, and then continuously recorded during 30 min of cycling at 0, 3, or 6 watts (W), followed by a 15-min resting period. REE determined by IC was compared with predictive formulas and correlated with several biomarkers. The energy cost of early exercise was compared between critically ill patients and healthy volunteers. Results: In patients, REE determined by IC was higher than predicted by Harris-Benedict (29 ± 31 %, p < 0.001) and Fleisch equations (23 ± 31 %, p < 0.001) but lower than predicted by the Faisy-Fagon equation for ventilated patients (16 ± 19 %, p < 0.05). Differences between Harris-Benedict predictions and IC determination were positively correlated with C-reactive protein (CRP) in patients with sepsis (r = 0.51, p = 0.003). During a similar exercise, VO 2 increase in patients was higher when compared with healthy volunteers at 3 W, close to significant at 6 W, and not present in the passive group. Conclusions: The critically ill have increased REE according to inflammation defined by CRP. Increased energy requirement for physical activity was only present for active exercise and seems to differ from that in the healthy population. For the exercise duration and intensity tested, nutritional adjustment is not indicated. © 2014 Springer-Verlag Berlin Heidelberg and ESICM
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