The effect of rosuvastatin alone or in combination with fenofibrate or omega-3 fatty acids on lipoprotein(a) levels in patients with mixed hyperlipidemia.

Introduction: Lipoprotein(a) [Lp(a)] is a strong, genetically determined, pathogenetic factor of atherosclerotic cardiovascular disease (ASCVD). The aim of this post-hoc analysis was to compare the effect of hypolipidemic treatment on Lp(a) levels of patients with mixed hyperlipidemia.
Material and Methods: We previously randomized patients with mixed hyperlipidemia (low-density lipoprotein [LDL-C] > 160 mg/dl and triglycerides > 200 mg/dl) to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or omega-3 fatty acids 2 g/day (RΩ group, n = 30). In the present post-hoc analysis, we included only the patients whose Lp(a) levels were assessed (16, 16 and 15 in the R, RF and RΩ groups, respectively). Lipid profile and Lp(a) were measured at baseline and after 3 months of treatment.
Results: Significant reductions in total cholesterol, LDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C) and triglyceride levels were observed in all groups. A significant increase in Lp(a) levels was noted in the R ( p = 0.017) and RF ( p = 0.029) groups, while no significant difference was seen in the RΩ group ( p = NS). Regarding Lp(a) elevations, no differences were found between groups. In the R group, a strong negative correlation between the changes in Lp(a) and LDL-C ( r = -0.500, p = 0.049) was observed, while a significant negative correlation between the changes in Lp(a) and triglycerides ( r = -0.531, p = 0.034) was noted in the RF group.
Conclusions: Rosuvastatin and/or fenofibrate treatment increases Lp(a) levels in patients with mixed hyperlipidemia. Novel therapies should target Lp(a) level reduction to decrease the residual ASCVD risk in patients with mixed hyperlipidemia.
Competing Interests: Theodosios D. Filippatos reports participation in advisory board for Lilly and lecture honoraria from Boehringer Ingelheim, Mylan, Astra Zeneca, Lilly, Recordati, Bausch Health, Servier, Viatris, Omega-Pharma and Innovis. Michael Kostapanos receives consultancy fees by GlaxoSmithKline (GSK) and Amarin Pharmaceuticals. He is also a Clinical Research Physician Director (as complementary worker by secondment) in the GSK Clinical Unit Cambridge. The remaining authors have no conflicts of interest to declare.
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