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 .)

Erich Schneider: The admiring disciple who did not become a follower

Erich Schneider, by 17 years a junior of Schumpeter’s, entered academics via a detour of teaching in a secondary school after obtaining his PhD in mathematics. Both his early teaching experience, and his background in mathematics exerted formative influences on his later work. No lesser figure than Schumpeter himself, whom he met while obtaining his academic teaching qualification at the University of Bonn, reportedly prophesized Schneider to become “the new preceptor of Germany” .This provides noteworthy evidence of both Schumpeter’s deep knowledge of human nature, and of the ironic side of his Viennese wittiness: while praeceptor Germaniae was an honorary title awarded by historians but to a few distinguished scholars of the middle ages, the term praeceptor had come to denote the rather modest position of adjunct teacher in grammar schools by the 19 th century. Indeed, Erich Schneider was to dominate economics teaching during the first post-war decades in Germany through his four volume introductory textbook (1947-62), but he left little lasting imprint on economic theory. In essence, he worked on all ‘big issues’ of the 1930ies such as market forms or the theory of production, eventually ventured into management science, and became an ardent advocate of Keynesianism. However, he did not follow the trails of economic change and innovation as one might have expected given the academic guidance obtained from Schumpeter. The absence of mathematical language for the analysis of dynamic phenomena during his days must have kept the trained mathematician from delving into Schumpeterian matters. Thus, through all of his academic life, Erich Schneider stayed a loyal disciple of Schumpeter’s, but cannot be considered a follower