Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Converter and Output Filter Topologies for STATCOMs

This chapter reviews different converter topologies and output filter configurations used in STATCOM applications. The output voltage and harmonic control of a STATCOM is obtained by individual control of each switch in the STATCOM. Several converter topologies can be considered for STATCOMs. The multi-pulse converters are developed using the most widely known 6-pulse configurations. The variations of multi-pulse converters such as 12-pulse, 24-pulse and 48-pulse that are built by combining 6-pulse converters via phase-shifting isolation transformers are introduced in terms of control methods and structures in this chapter. On the other hand, the multilevel converters are considered to be used in recent STATCOM topologies as an alternative to the multi-pulse configurations, owing to their multi MVA switching capability that is inherited from series or parallel connection of converter cells. The diode clamped, flying capacitor, and cascaded H-bridge configurations of multilevel converters, that are the most widely known topologies, are comprehensively introduced in this chapter. The multilevel converter topologies provide several advantages such as harmonic elimination, lower electromagnetic interference, better output waveforms, and increased power factor correction (PFC) capabilities together. Furthermore, each switch can be controlled individually to robustly tackle the unbalanced load operations even in higher switching frequencies relatively to the multi-pulse configuration. The related subsections propose control and operation properties of converters besides introducing the main topological issues. The filtering requirements of STATCOM are particularly considered in this chapter where the passive and active filters are introduced in detail. The passive filters designed with reactive components such as individual L and C or their combinations as LC or LCL are surveyed according to design and analytical criteria. Besides, active power filters (APFs) that provide several feedback control methods increasing the efficiency and controllability are discussed in the following part. The control methods of STATCOM converters are introduced in a separate section where the recent control approaches and analytical calculations required are presented in detail. The block diagrams of the industrial STATCOM applications are also discussed