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 .)

Low Susceptibility of Invasive Red Lionfish (Pterois volitans) to a Generalist Ectoparasite in Both Its Introduced and Native Ranges

Escape from parasites in their native range is one of many mechanisms that can contribute to the success of an invasive species. Gnathiid isopods are blood-feeding ectoparasites that infest a wide range of fish hosts, mostly in coral reef habitats. They are ecologically similar to terrestrial ticks, with the ability to transmit blood-borne parasites and cause damage or even death to heavily infected hosts. Therefore, being highly resistant or highly susceptible to gnathiids can have significant fitness consequences for reef-associated fishes. Indo-Pacific red lionfish (Pterois volitans) have invaded coastal habitats of the western tropical and subtropical Atlantic and Caribbean regions. We assessed the susceptibility of red lionfish to parasitic gnathiid isopods in both their native Pacific and introduced Atlantic ranges via experimental field studies during which lionfish and other, ecologically-similar reef fishes were caged and exposed to gnathiid infestation on shallow coral reefs. Lionfish in both ranges had very few gnathiids when compared with other species, suggesting that lionfish are not highly susceptible to infestation by generalist ectoparasitic gnathiids. While this pattern implies that release from gnathiid infestation is unlikely to contribute to the success of lionfish as invaders, it does suggest that in environments with high gnathiid densities, lionfish may have an advantage over species that are more susceptible to gnathiids. Also, because lionfish are not completely resistant to gnathiids, our results suggest that lionfish could possibly have transported blood parasites between their native Pacific and invaded Atlantic ranges