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

• Published in: Cardiovascular therapeutics Vol. 32; no. 4; pp. 139 - 146
• Main Authors: Kei, Anastazia, Tellis, Constantinos, Liberopoulos, Evangelos, Tselepis, Alexandros, Elisaf, Moses
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01.08.2014
• Subjects: Aged; Apolipoprotein B-100 - blood; Atorvastatin Calcium; Bilirubin - blood; Biomarkers - blood; Dinoprost - analogs & derivatives; Dinoprost - blood; Drug Therapy, Combination; Dyslipidemias - blood; Dyslipidemias - diagnosis; Dyslipidemias - drug therapy; F2‐Isoprostanes; Female; fenofibrate; Fenofibrate - administration & dosage; Fenofibrate - adverse effects; Fluorobenzenes - administration & dosage; Fluorobenzenes - adverse effects; Greece; Heptanoic Acids - administration & dosage; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - adverse effects; Indoles - administration & dosage; Indoles - adverse effects; Lipoproteins, LDL - blood; Male; Middle Aged; mixed dyslipidemia; Niacin - administration & dosage; Niacin - adverse effects; nicotinic acid/laropiprant; oxidative stress; Oxidative Stress - drug effects; oxidized LDL; Prospective Studies; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrroles - administration & dosage; rosuvastatin; Rosuvastatin Calcium; Simvastatin - administration & dosage; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Time Factors; Treatment Outcome; Uric Acid - blood; Greece; nicotinic acid/laropiprant; F2-Isoprostanes; fenofibrate; oxidized LDL; rosuvastatin; oxidative stress; mixed dyslipidemia
• ISSN: 1755-5914; 1755-5922
• DOI: 10.1111/1755-5922.12072

Summary Introduction 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.