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 .)

Individual change in methylphenidate use in a national sample of children aged 2 to 11 years

Objectives: To determine methylphenidate use in children aged 2 to 13 years. To provide age- and sex-specific estimates of methylphenidate initiation and cessation during a 2-year period. // Method: Data from 2 cycles of a Canadian household survey yielded a sample of over 10 000 children aged 2 to 11 years at Cycle 1 who continued to participate at Cycle 2. We used logit modelling to estimate Cycle 2 methylphenidate use, methylphenidate use over a 2-year period, and methylphenidate initiation and cessation from Cycles 1 to 2. // Results: In 1996 and 1997, methylphenidate use ranged from 0.32% to 6.31% among children aged 4 to 13 years. School-aged boys were more likely than girls to use methylphenidate. Odds were greater for boys aged 6 to 7 years than for boys aged 4 to 5 years; they were also greater for boys aged 10 to 11 years than for boys aged 12 to 13 years. Almost 1% of children used methylphenidate at both data cycles. Odds of Cycle 2 methylphenidate use were 135 times greater for children using methylphenidate at Cycle 1, compared with nonusers. Methylphenidate initiation ranged from 0.20% to 3.34%, and school-aged boys had higher initiation rates than girls. Cessation rates ranged from 18% to78%, and there were no statistically significant differences by age and sex. // Conclusions: Methylphenidate prevalence findings are consistent with past studies. We found an age-by-sex interaction on methylphenidate use. We also found both continuity and discontinuity in methylphenidate use.The study was conducted at the National Longitudinal Survey of Children and Youth Research Centre in Children’s Behaviour Development, University of Montreal. The study was funded by the Applied Research Branch of Human Resources Development Canada (contract 9137-99-0080)