Effect of hypolipidemic treatment on emerging risk factors in mixed dyslipidemia: a randomized pilot trial

Background The effects of different hypolipidemic treatment strategies on emerging atherosclerosis risk factors remain unknown. Materials and methods This is a prespecified analysis of a prospective, randomized, open-label, blinded end point (PROBE) study (ClinicalTrials.gov identifier: NCT01010516). Patients (n=100) with mixed dyslipidaemia on a standard statin dose 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) or to add-on-statin micronized fenofibrate for a total of 3months. Results Following 3months of treatment, low-density lipoprotein (LDL) particle size increased equally in all groups. Similarly, all treatments were associated with comparable small dense LDL cholesterol reduction. Apolipoprotein B levels decreased by 15%, 7% and 4% in the rosuvastatin, add-on ER-NA/LRPT and add-on fenofibrate group, respectively (P<0 center dot 01 for all compared with baseline, P<0 center dot 01 for all comparisons between groups). Only add-on ER-NA/LRPT was associated with lipoprotein (a) reduction (26%, P<0 center dot 01 compared with baseline). Rosuvastatin monotherapy and add-on ER-NA/LRPT groups were associated with 56% and 24% reduction in high-sensitivity C-reactive protein levels (hsCRP), respectively (P<0 center dot 01 compared with baseline), while add-on fenofibrate was not associated with changes in hsCRP concentration. Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity decreased similarly in both rosuvastatin and add-on fenofibrate groups, while add-on ER-NA/LRPT was associated with a more pronounced Lp-PLA2 activity reduction. ER-NA/LRPT was associated with more side effects compared with rosuvastatin and add-on fenofibrate. Conclusions Add-on ER-NA/LRPT followed by switch to the highest dose rosuvastatin were associated with more pronounced beneficial modifications in emerging cardiovascular risk factors compared with add-on fenofibrate in patients with mixed dyslipidaemia.