The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

(R)‐1‐(4‐chloro‐2‐(3‐methyl‐1H‐pyrazol‐1‐yl)phenyl)‐2,2,2‐trifluoroethan‐1‐ol [(R)‐2] is a key chiral intermediate in the synthesis of telotristat ethyl, an anti‐carcinoid syndrome drug. However, the synthetic methods for (R)‐2 mainly include chemical reductions, rarely involving biocatalysis or bioreduction until now. Here, we report a method for obtaining (R)‐2 by biocatalytic reduction of corresponding prochiral acetophenone (1) with bulky o‐substitution using recombinant Lactobacillus fermentum short‐chain dehydrogenase/reductase 1 (LfSDR1) as a biocatalyst. Further engineering of LfSDR1 variants could access asymmetric reduction of 1 and yield (R)‐2 with a >99% ee and a >99% conversion. In addition, through the test of different co‐solvents and a series of initial substrate concentrations, substrate 1 with the concentration of 60 g/L can be completely converted into (R)‐2 on a preparative scale (1.13 g, 3.93 mmol, 75.6% isolated yield) in 24 hours. This study presents an efficient enzymatic process for the biocatalytic synthesis of key chiral intermediate (R)‐2 in the synthesis of telotristat ethyl.

Contrast-induced nephropathy (CIN) develops after the injection of iodinated contrast media. This is a post hoc analysis of the data obtained from the TRUST study, which was a prospective, multicentre, observational study conducted to evaluate the safety and tolerability of the contrast medium iopromide in patients undergoing cardiac catheterization from August 2010 to September 2011 in China, conducted to explore the current status, trends and risk predictors of hydration treatment. The status of hydration to prevent CIN in each patient was recorded. Of the total 17,139 patients from the TRUST study (mean age, 60.33 ± 10.38 years), the overall hydration usage was 46.1% in patients undergoing percutaneous coronary intervention (PCI) and 77.4%, 51.7%, and 48.5% in patients with pre-existing renal disease, diabetes mellitus, and hypertension, respectively. The proportion of hydration use increased from 36.5% to 55.5% from August 2010 to September 2011, which was independently associated with risk predictors like older age, pre-existing renal disease, hypertension, diabetes mellitus, prior myocardial infarction, ST segment elevation MI, high contrast dose, multi-vessel disease and reduced LVEF (<45%). Overall, the usage of intravenous hydration treatment for patients with a high risk of CIN following PCI was high in China.

No abstract