title: Effect of switch to the highest dose of rosuvastatin versus add-on-statin fenofibrate versus add-on-statin nicotinic acid/laropiprant on oxidative stress markers in patients with mixed dyslipidemia.
abstract: BACKGROUND
  Oxidative stress plays an important role in atherosclerosis. Both F2-isoprostane (8-iso-PGF2a) and oxidized low-density lipoprotein (ox-LDL) have emerged as biomarkers of oxidative stress and have been proposed as useful biomarkers that could potentially be used as indicators of cardiovascular disease.
  
  
  METHODS
  This is a prespecified analysis of a prospective, randomized, open-label, blinded endpoint (PROBE) study (ClinicalTrials.gov identifier: NCT01010516). Patients (N = 100) with mixed dyslipidemia on a standard statin dose (10-40 mg simvastatin or 10-20 mg atorvastatin or 5-10 mg rosuvastatin) who had not achieved lipid targets were randomized to switch to the highest dose of rosuvastatin (40 mg/day) or to add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks) or to add-on-statin micronized fenofibrate (200 mg/day) for a total of 3 months. Levels of plasma and urine F2-isoprostane and plasma ox-LDL were assessed at baseline and 3 months later.
  
  
  RESULTS
  Plasma F2-isoprostane levels decreased similarly in all groups. On the other hand, both ox-LDL and urine F2-isoprostane levels decreased similarly in the add-on ER-NA/LRPT and rosuvastatin monotherapy group, while a less pronounced decrease was observed in the add-on fenofibrate group.
  
  
  CONCLUSIONS
  All treatment interventions reduced the concentration of the assessed oxidative stress markers, but the reduction was more pronounced in the add-on ER-NA/LRPT and rosuvastatin monotherapy groups, compared with add-on fenofibrate. Specifically designed studies should address the abovementioned risk factors modulation in terms of cardiovascular risk.
authors.affiliation: Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece.
authors.forename: Anastazia
authors.initials: A
authors.lastname: Kei
authors.forename: Constantinos
authors.initials: C
authors.lastname: Tellis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Liberopoulos
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tselepis
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
mesh_terms: D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood; D000069059:Atorvastatin; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage* / Q000009:adverse effects; D005464:Fluorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D006115:Greece; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D015415:Biomarkers; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007211:Indoles; D008077:Lipoproteins, LDL; C518174:MK-0524; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C099252:oxidized low density lipoprotein; D009525:Niacin; D014527:Uric Acid; C075750:8-epi-prostaglandin F2alpha; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; D015237:Dinoprost; D001663:Bilirubin; D011345:Fenofibrate
keywords: F2-Isoprostanes; fenofibrate; mixed dyslipidemia; nicotinic acid/laropiprant; oxidative stress; oxidized LDL; rosuvastatin