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 .)

Une mise à jour sur les agents neurotoxiques: ce que le premier répondant, l’anesthésiologiste et l’intensiviste doivent savoir

The purpose of this review article is to familiarize first responders, anesthesiologists, and intensivists with the medical management of patients exposed to nerve agents. This review is based on the current medical literature available to the general medical community. Nerve agents are some of the deadliest substances known to humanity. Though they kill primarily via muscle paralysis, which leads to respiratory arrest, these agents affect virtually every organ system in the body. Their primary mechanism of action is the body-wide inhibition of cholinesterases. This inhibition leads to the accumulation of acetylcholine, stimulating both nicotinic and muscarinic receptors. After decontamination, the primary treatment is with atropine to control muscarinic symptoms and with oximes to reactivate the cholinesterases and treat the nicotinic symptoms. Atropine doses can be much higher than conventionally used. Seizures are generally best treated with benzodiazepines. Patients with substantial exposure may require ventilatory and intensive care unit support for prolonged periods of time. While it is unlikely that most medical practitioners will ever encounter nerve agent poisoning, it is critical to be aware of the presenting symptoms and how best to treat patients exposed to these deadly agents. History has shown that rapid medical treatment can easily mean the difference between life and death for a patient in this situation