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

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. 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 (10-40mg simvastatin or 10-20mg atorvastatin or 5-10mg rosuvastatin) who had not achieved lipid targets were randomized to switch to the highest dose of rosuvastatin (40mg/day) or to add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) (1000/20mg/day for the first 4weeks followed by 2000/40mg/day for the next 8weeks) or to add-on-statin micronized fenofibrate (200mg/day) for a total of 3months. Levels of plasma and urine F2-isoprostane and plasma ox-LDL were assessed at baseline and 3months later. 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. 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.