Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials.

AimsThis analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.Materials and methodsData from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo-controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe-controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL-C.ResultsLDL-C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non-MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non-MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) and HDL-C. Overall, the percentage change at Week 24 in LDL-C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection-site reactions occurred more frequently in alirocumab vs control groups.ConclusionsAcross study pools, alirocumab-associated reductions in LDL-C, apolipoprotein B, and non-HDL-C were significant vs control, and did not vary by MetS status

Electrochemical Reduction of Intermediates in the Vitamin B6 Production. I. Reduction of 2-Methyl-3-nitro-4-methoxymethyl- 5-cyano-6-chloropyridine

2-Methy 1-3-ni tro-4-metoxymethy 1-5-cyano-6-chloropyridine (I) was reduced on a mercury-pool cathode in an electrolytic cell fitted with a diaphragm. The catholyte consisted of a mixture of acetiC acid and hydrochloric acid and the anolyte was dilute hydrochloric acid. At a potential of - 0.5 V vs. SCE. compound I was reduced to 2-methy 1-3-amino-4-methoxymethy 1-5-cyano-6-chloropyridine (II). Compound II was reduced at a potential of -1.1 V vs. SCE. to give 2,4-dimethyl-3-amino-5-cyanopyridine (Ill). Compound III was reduced at constant current density to 2,4-dimethyl-3-amino- 5-aminomethylpyridine (IV). The influence of several factors (depolarizer concentration, electrolyte concentration and temperature) on yield of products was examined in each step. Polarograms were recorded with compounds I, II and III, and the character of limiting currents was assessed using the usual criteria