High-Dose Simvastatin Exhibits Enhanced Lipid-Lowering Effects Relative to Simvastatin/Ezetimibe Combination Therapy
| Autor: | Theresa L. Pedersen, Oliver Fiehn, Craig E. Wheelock, Stuart G. Snowden, Jesper Z. Haeggström, John W. Newman, Matej Orešič, Fabio Luiz D’Alexandri, Tuulia Hyötyläinen, Magnus Settergren, Dmitry Grapov, John Pernow |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Simvastatin Ceramide Combination therapy Hypercholesterolemia Ezetimibe Simvastatin Drug Combination Pharmacology Ceramides Drug Administration Schedule Article chemistry.chemical_compound Double-Blind Method Ezetimibe Genetics medicine Humans Triglycerides Genetics (clinical) Aged Phosphatidylethanolamine Analysis of Variance Cholesterol Anticholesteremic Agents Discriminant Analysis Cholesterol LDL Lipid signaling Middle Aged Sphingomyelins Drug Combinations Treatment Outcome chemistry Phosphatidylcholines Azetidines Female lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine Sphingomyelin medicine.drug |
| Zdroj: | Circulation: Cardiovascular Genetics. 7:955-964 |
| ISSN: | 1942-3268 1942-325X |
| DOI: | 10.1161/circgenetics.114.000606 |
| Popis: | Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy ( R 2 Y =0.74; Q 2 =0.66; cross-validated ANOVA P =7.0×10 −8 ) and combination therapy ( R 2 Y =0.67; Q 2 =0.54; cross-validated ANOVA P =2.6×10 −5 ). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks ( R 2 Y =0.65; Q 2 =0.61; cross-validated ANOVA P =5.4×10 −8 ). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups ( q q =0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine ( q =0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|