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

SUMMARYIntroduction: 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 addon 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.

Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A double-blind, randomized, placebo-controlled study

“…The sign of increased oxidative stress in the fenofibrate treatment group was surprising in light of previous findings of reduced plasma hydroxylated C18fatty acids, oxidized LDL, 57 and F2-isoprostane levels. 58 A potential explanation for this is that we measured F2isoprostanes in urine because the effect of fenofibrate on F2-isoprostanes was shown to be less pronounced in urine than in plasma. 58 As previously shown, 59 PPARa agonism/fenofibrate treatment increased plasma FGF21 levels in humans.…”

“…58 A potential explanation for this is that we measured F2isoprostanes in urine because the effect of fenofibrate on F2-isoprostanes was shown to be less pronounced in urine than in plasma. 58 As previously shown, 59 PPARa agonism/fenofibrate treatment increased plasma FGF21 levels in humans. Similarly, in line with previous results in patients with NAFLD, 60 OM-3CA treatment reduced FGF21 levels; this may indicate an improved hepatic metabolism, given that high FGF21 levels are associated with NAFLD and mitochondrial dysfunction.…”

Antioxidant properties of drugs used in Type 2 diabetes management: could they contribute to, confound or conceal effects of antioxidant therapy?

“…C max = 709 ± 221 ng/ ml AUC = 6120 ± 2171 ng.h/ml [41] isoprostanes as well as to increase concentrations of an erythrocyte antioxidant enzyme, superoxide dismutase (SOD) [59,62,66,69,81,87,93,95]. Although both in vitro and in vivo studies provide evidence of the antioxidant properties of statins, conflict exists with regard to the effect of statins on plasma tocopherols (vitamin E).…”

No effects of atorvastatin (10mg/d or 80mg/d) on nitric oxide, prostacyclin, thromboxane and oxidative stress in type 2 diabetes mellitus patients of the DALI study

“…However, the aggressive atorvastatin dose of 80 mg/d increased the urinary 8-iso-PGF 2␣ excretion, yet this increase failed very nearly statistical significance (P = 0.07). Thus far, several groups have investigated the effect of atorvastatin and other statins on oxidative stress, including 8-iso-PGF 2␣ , in different diseases and conditions including hypercholesterolemia with diverging results [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64].…”