Title
Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: Investigating differential effects among statins
Author
Bergheanu, S.C.
Reijmers, T.
Zwinderman, A.H.
Bobeldijk, I.
Ramaker, R.
Liem, A.-H.
van der Greef, J.
Hankemeier, T.
Jukema, J.W.
TNO Kwaliteit van Leven
Publication year
2008
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.
Subject
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
To reference this document use:
http://resolver.tudelft.nl/uuid:314b968f-c3d9-4874-acd1-0a8b47acba9c
DOI
https://doi.org/10.1185/03007990802321709
TNO identifier
240991
ISSN
0300-7995
Source
Current Medical Research and Opinion, 24 (9), 2477-2487
Document type
article