Efficacy and Safety of Rosuvastatin and Fenofibric Acid Combination Therapy versus Simvastatin Monotherapy in Patients with Hypercholesterolemia and Hypertriglyceridemia: A Randomized, Double-Blind Study.

Objectives: To evaluate the efficacy and safety of fixed-dose combinations of rosuvastatin and fenofibric acid (rosuvastatin/fenofibric acid) compared with simvastatin in patients with high levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Background: Combination therapy with a statin and a fibrate is one of the treatment options to manage multiple lipid abnormalities in patients with hypercholesterolemia and elevated TGs. Methods: In this randomized, double-blind study, patients (n = 474) with LDL-C ≥160mg/dL and ≤240mg/dL and TG ≥150mg/dL and <400mg/dL were treated for 8 weeks with simvastatin 40 mg, rosuvastatin/fenofibric acid 5mg/135 mg, rosuvastatin/fenofibric acid 10 mg/135 mg, or rosuvastatin/ fenofibric acid 20 mg/135 mg. Primary and secondary variables were mean percent changes in LDL-C comparing rosuvastatin/fenofibric acid 20mg/135mg with simvastatin 40 mg and rosuvastatin/fenofibric acid 10 mg/135mg and rosuvastatin/fenofibric acid 5mg/135mg with simvastatin 40 mg, respectively. Additional efficacy variables included non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein (Apo) B, HDL-C, TG, and high-sensitivity C-reactive protein (hsCRP). Safety was evaluated based on data collected for adverse events (AEs), physical and electrocardiographic examinations, vital sign measurements, and clinical laboratory tests. Results: Significantly greater reductions in LDL-C levels from baseline values were observed with the combination of rosuvastatin/fenofibric acid 20mg/135mg (-47.2%, p< 0.001), rosuvastatin/fenofibric acid 10 mg/135mg (-46.0%, p< 0.001), and rosuvastatin/fenofibric acid 5mg/135mg (-38.9%, p= 0.007) than with simvastatin 40mg (-32.8%). Significant (p < 0.04 for all comparisons) improvements in non-HDL-C, ApoB, HDL-C, TG, and hsCRP levels were also observed with each of the rosuvastatin/fenofibric acid doses as compared with simvastatin 40 mg. Treatment-related AEs and discontinuations due to AEs were similar across groups. The incidence of serious AEs was 0% with simvastatin 40 mg, 3.4% with rosuvastatin/ fenofibric acid 5mg/135 mg, 0.8% with rosuvastatin/fenofibric acid 10mg/135 mg, and 2.5% with rosuvastatin/ fenofibric acid 20 mg/135 mg. No cases of rhabdomyolysis or drug-related myopathy were reported. Conclusion: In patients with high LDL-C and TGlevels, combination treatment with rosuvastatin/fenofibric acid was well tolerated, and each of the rosuvastatin/fenofibric acid doses produced greater reductions in LDL-C and improvements in other efficacy parameters, compared with simvastatin 40 mg. [ABSTRACT FROM AUTHOR]