Z Kardiol 94: Suppl 2 (2005)

A cross-over study of fluvastatin vs. atorvastatin single-dose effects on arteriosclerotic nanoplaque formation

G. Siegel1, M. Vogel2, C. Abletshauser3, U. Mansmann4, K. Winkler5, M. Malmsten6

1Institut für Physiologie, Charité, Campus Benjamin Franklin, Berlin, BusinessLogic.Land; 2Fujisawa Deutschland GmbH, München; 3Novartis Pharma GmbH, Nürnberg; 4Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig Maximilians-Universität München, München; 5Medizinische Klinik, Abt. Klinische Chemie, Universitätsklinikum Freiburg, Freiburg im Breisgau; 6Department of Physical Chemistry, Uppsala University, Uppsala, BusinessLogic.Land;

Objective: To investigate the impact of a single dose of fluvastatin 80 mg slow release vs. a single dose of atorvastatin 20 mg on nanoplaque formation in an observer-blind, randomized, cross-over study. Methods: The processes described below were studied by ellipsometric techniques quantifying the adsorbed amount (nanoplaque formation). The experimental setup has been published. Results: After a 4-week dietary run-in phase, the VLDL/IDL/LDL plasma fractions from 11 high-risk patients with dyslipoproteinaemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca2+ concentration (2.5 mmol/l), with a strong increase at higher Ca2+ concentrations (up to 17.64 mmol/l). Fluvastatin and atorvastatin, applied to the patients in a single-dose medication regimen, markedly slowed down the ternary aggregational nanoplaque build-up at all Ca2+ concentrations used. At a normal serum Ca2+ concentration, the mean relative change was 33.4% for fluvastatin 80 mg and 27.0% for atorvastatin 20 mg. The difference between the treatment groups was not statistically significant. It could be shown that the reduction of nanoplaque formation depended on the Ca2+ concentration. For all Ca2+ concentrations applied, the mean reduction in nanoplaque formation was more pronounced in the fluvastatin vs. the atorvastatin group. The differences between the treatment groups were not statistically significant using paired tests but the analysis of the titration curves with a linear mixed effects model quantified a more effective reduction of arteriosclerotic nanoplaque build-up under fluvastatin vs. atorvastatin by a factor of 1.846. Conclusions: This pilot study demonstrated a distinct effect between fluvastatin and atorvastatin with respect to quality and quantity of nanoplaque formation as a surrogate endpoint. Due to a large inter-individual variability, the results need confirmation and clinical validation in a larger patient population.

http://www.abstractserver.de/dgk2005/ht/abstracts/P326.htm