title: The effects of raloxifene and simvastatin on plasma lipids and endothelium.
abstract: OBJECTIVE
  Raloxifene is a selective estrogen receptor modulator and an attractive alternative to estrogen replacement as it obviates the need for a progestin and does not increase C-reactive protein levels. We compared the effects of simvastatin and raloxifene treatments on the lipid profile, the levels of adhesion molecules and the endothelium dependent and independent vasoreactivity.
  
  
  METHODS
  We treated 12 postmenopausal women with hypercholesterolemia and coronary artery disease with raloxifene 60 mg/day and simvastatin 20 mg/day in a randomized, double-blind, crossover study. Each treatment period was 8 weeks long with a 4-week washout interval. Plasma lipids and cellular adhesion molecules were evaluated and peripheral blood flow studies with venous occlusion plethysmography were performed.
  
  
  RESULTS
  Both simvastatin and raloxifene significantly reduced total [33% (27-40), 12% (0-24)] and LDL [44% (36-52), 16% (0-33)] cholesterol compared to baseline values (p < 0.05) but simvastatin was more effective than raloxifene (p < 0.005). None of the treatments had any significant effect on HDL cholesterol and triglyceride levels. Only raloxifene significantly reduced Lp(a) [18% (1-36)] and ICAM-1 [17% (8-25)] and VCAM-1 [24% (15-33)] plasma levels compared to baseline (p = 0.019, p < 0.0001 and p = 0.003, respectively). Hyperemic blood flow response on raloxifene was significantly higher compared to baseline [52% (0-105)], (p < 0.05), whereas no significant change was noted on simvastatin. Endothelium independent blood flow induced by nitroglycerine was not influenced by either active treatment.
  
  
  CONCLUSIONS
  Raloxifene administration is associated with lower ICAM-1, VCAM-1 and Lp(a) plasma levels and enhanced endothelium dependent dilation compared to simvastatin although simvastatin is more powerful in total and LDL cholesterol reduction.
authors: 2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. elbee@ath.forthnet.gr
authors: Eftihia
authors: E
authors: Sbarouni
authors: Panagiota
authors: P
authors: Flevari
authors: Christos
authors: C
authors: Kroupis
authors: Zenon S
authors: ZS
authors: Kyriakides
authors: Katerina
authors: K
authors: Koniavitou
authors: Dimitrios Th
authors: DT
authors: Kremastinos
mesh_terms: D000368:Aged; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D019821:Simvastatin