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Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: Investigating differential effects among statins

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Author: Bergheanu, S.C. · Reijmers, T. · Zwinderman, A.H. · Bobeldijk, I. · Ramaker, R. · Liem, A.-H. · Greef, J. van der · Hankemeier, T. · Jukema, J.W.
Type:article
Date:2008
Institution: TNO Kwaliteit van Leven
Source:Current Medical Research and Opinion, 9, 24, 2477-2487
Identifier: 240991
doi: doi:10.1185/03007990802321709
Keywords: Biology · Atorvastatin · Cardiovascular risk · Phosphatidylcholines · Rosuvastatin · Sphingomyelins · Atorvastatin · Cholesterol · High density lipoprotein cholesterol · Hydroxymethylglutaryl coenzyme A reductase inhibitor · Low density lipoprotein cholesterol · Phosphatidylcholine · Rosuvastatin · Sphingomyelin · Triacylglycerol · Adult · Aged · Article · Cardiovascular risk · Cholesterol blood level · Clinical trial · Controlled clinical trial · Controlled study · Coronary artery disease · Drug dose increase · Drug efficacy · Drug megadose · Female · Human · Lipid blood level · Lipid metabolism · Lipidomics · Liquid chromatography · Low drug dose · Major clinical study · Male · Mass spectrometry · Multicenter study · Phase 3 clinical trial · Randomized controlled trial · Therapy effect · Treatment outcome · Chromatography, Liquid · Dose-Response Relationship, Drug · Fluorobenzenes · Heptanoic Acids · Humans · Hydroxymethylglutaryl-CoA Reductase Inhibitors · Lipids · Mass Spectrometry · Prospective Studies · Pyrimidines · Pyrroles · Sulfonamides

Abstract

Objective: Lipid profiling (lipidomics) may be useful in revealing detailed information with regard to the effects on lipid metabolism, the cardiovascular risk and to differentiate between therapies. The aims of the present study were to: (1) analyze in depth the lipid changes induced by rosuvastatin and atorvastatin at different dosages; (2) compare differences between the two drugs with respect to the lipid profile change; (3) relate the findings with meaningful pathological mechanisms of coronary artery disease. Research design and methods: Liquid chromatography-mass spectrometry was applied to obtain the metabolite profiles of plasma samples taken from a prospectively defined subset (n = 80) of participants in the RADAR study where a randomly assigned treatment with rosuvastatin or atorvastatin in increasing dosages was administered during an 18-week period. Results: A number of sphingomyelins (SPMs) and phosphatidylcholines (PGs) correlate with the different effects of the two statins on the LDL-C/HDL-C ratio. Rosuvastatin increased the plasma concentration of PCs after 6 and 18 weeks, while atorvastatin reduced the plasma concentrations of PCs at both timepoints and dosages (p<0.01 for between-treatment comparison). Both atorvastatin and rosuvastatin lowered plasma SPMs concentrations, but atorvastatin demonstrated a more pronounced effect with the highest dose (p = 0.03). Rosuvastatin resulted in a significantly more effective lowering of the [SPMs/(SPMs + PCs)] ratio than atorvastatin at any dose/timepoint (p<0.05), a ratio reported to be of clinical importance in coronary artery disease. Conclusions: The lipidomic technique has revealed that statins are different with regards to the effect on detailed lipid profile. The observed difference in lipids may be connected with different clinical outcomes as suggested by the [SPMs/(SPMs + PCs)] ratio. © 2008 Informa UK Ltd.