Effect of hypolipidemic treatment on emerging risk factors in mixed dyslipidaemia: a randomized pilot tria

Background The effects of different hypolipidemic treatment strategies on emerging atherosclerosis riskfactors remain unknown.Materials and 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 dyslipidaemiaon a standard statin dose who had not achieved lipid targets were randomized to switch to the highest dose ofrosuvastatin (40 mg/day) or to add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) or toadd-on-statin micronized fenofibrate for a total of 3 months.Results Following 3 months of treatment, low-density lipoprotein (LDL) particle size increased equally in allgroups. 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-onfenofibrate group, respectively (P < 0 01 for all compared with baseline, P < 0 01 for all comparisons betweengroups). Only add-on ER-NA/LRPT was associated with lipoprotein (a) reduction (26%, P < 0 01 compared withbaseline). 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 01 compared with baseline),while add-on fenofibrate was not associated with changes in hsCRP concentration. Lipoprotein-associatedphospholipase 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/LRPTwas 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 withmore pronounced beneficial modifications in emerging cardiovascular risk factors compared with add-onfenofibrate in patients with mixed dyslipidaemia.