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 .)

Two global ensemble M5.95+ seismicity models obtained from the combination of interseismic strain rates and earthquake-catalogue data

Contains two global earthquake-rate forecasts developed by Bayona et al. (2021) to be prospectively evaluated by the Collaboratory for the Study of Earthquake Predictability (CSEP). The Tectonic Earthquake Activity Model (TEAM) is a geodetic-based model using Version 2.1 of the Global Strain Rate Map (GSRM2.1; Kreemer et al., 2014), while the World Hybrid Earthquake Estimates based on Likelihood scores (WHEEL) is a model obtained from a multiplicative log-linear combination of TEAM with the Smoothed Seismicity (KJSS) model of Kagan and Jackson (2011). Earthquake densities are expressed as number of M5.95+ events per unit 0.1o cell per year. The forecasts are stored in tab separated value files, with the following fields (the first row of data is shown as an example): lon_minlon_maxlat_minlat_maxdepth_mindepth_max5.956.05...-180.0-179.9-90.0-89.90.070.04.95e-113.97e-11... Data and forecasts are described in detail in the following publications: Bayona, J.A., Savran, W., Strader, A., Hainzl, S., Cotton, F. and Schorlemmer, D., 2021. Two global ensemble seismicity models obtained from the combination of interseismic strain measurements and earthquake-catalogue information. Geophysical Journal International, 224(3), pp.1945-1955. Kreemer, C., Blewitt, G. and Klein, E.C., 2014. A geodetic plate motion and Global Strain Rate Model. Geochemistry, Geophysics, Geosystems, 15(10), pp.3849-3889. Kagan, Y.Y. and Jackson, D.D., 2011. Global earthquake forecasts. Geophysical Journal International, 184(2), pp.759-776

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

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