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 .)

Asset Valuation and Production Efficiency in an Overlapping-Generations Model with Production Shocks.

This paper extends the Cass criterion for production efficiency to include uncertainty and uses it to show that a stock-market equilibrium in an overlapping-generations model with production uncertainty is efficient. It also develops a no-bubbles asset-pricing formula. Results are compared with W. A. Brock's (1982) infinite-lived consumer model and it is shown that the stock-market equilibrium in the overlapping-generations model has precisely the same asset valuation as Brock's infinitely-lived agent model. Copyright 1992 by The Review of Economic Studies Limited.

The Identification of Spurious Lyapunov Exponents in Jacobian Algorithms

The method of reconstructing an n-dimensional system from observations is to form vectors of m consecutive observations, which for m 2n, is generically an embedding. This is Takens's result. The Jacobian methods for Lyapunov exponents utilize a function of m variables to model the data, and the Jacobian matrix is constructed at each point in the orbit of the data. When embedding occurs at dimension m = n, the Lyapunov exponents of the reconstructed dynamics are the Lyapunov exponents of the original dynamics. However, if embedding only occurs for an m > n, then the Jacobian method yields m Lyapunov exponents, only n of which are the Lyapunov exponents of the original system. The problem is that as currently used, the Jacobian method is applied to the full m-dimensional space of the reconstruction, and not just to the n-dimensional manifold that is the image of the embedding map. Our examples show that it is possible to obtain spurious Lyapunov exponents that are even larger than the largest Lyapunov exponent of the original system.

Risk and Return in a Dynamic Asset Pricing Model

In this study we combine the dynamic programming method with the projection methods for solving stochastic growth models. One of the inconveniences of Judd's projection technique is that finding a good initial guess is not that easy or it is time costly especially when the dimensionality of the problem is high. Secondly, there is no theoretical assurance that projection technique converges to the true policy function. First we use the dynamic programming method to obtain an approximate solution for the policy function. Since the approximate solution is in the vicinity of the true solution, we use those coefficients as the initial guess for the projection method. Then we use Judd's projection method to find an exact solution for the policy function. Once we find the exact solution for the policy function we check whether or not projection method converged to the true policy function. We do that by using the dynamic programming method to test whether the policy function satisfies the Bellman equation.