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Background: Statins are the standard-of-care therapy for reducing low-density lipoprotein cholesterol (LDL-C) levels; however, combination with other lipid-modifying agents may be necessary to normalize lipid profiles in patients with mixed dyslipidemia who, in addition to high LDL-C, also have high triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C). Objective: This study aimed to evaluate the 1-year efficacy and safety of rosuvastatin in combination with fenofibric acid in a subgroup of patients treated for 12 weeks with rosuvastatin 10mg + fenofibric acid 135mg and subsequently treated for up to 52 weeks with rosuvastatin 20 mg+ fenofibric acid 135 mg. Methods: The efficacy and safety of combination therapy with rosuvastatin + fenofibric acid were demonstrated in a 12-week controlled study (NCT00300482) of patients with mixed dyslipidemia who were randomized to rosuvastatin 10, 20, or 40 mg, fenofibric acid 135 mg, or rosuvastatin 10 or 20mg + fenofibric acid 135 mg. All patients who completed the controlled study were eligible to enroll in a subsequent 52-week open-label extension study (NCT00300430) and received rosuvastatin 20mg + fenofibric acid 135 mg. The present post hoc analysis evaluated patients who were treated with rosuvastatin 10mg + fenofibric acid 135mg in the controlled study and received rosuvastatin 20mg + fenofibric acid 135mg in the open-label extension study. The study was carried out at investigative sites in the US (including Puerto Rico) and Canada. Patients included in the study were men and women ≥18 years of age with mixed dyslipidemia, defined as TG ≥150mg/dL, LDL-C ≥130mg/dL, and HDL-C <40/50mg/dL for men/women (at screening in the controlled trial). Efficacy variables included mean percentage changes in LDL-C, HDL-C, non-HDL-C, and apolipoprotein B (ApoB), andmedian percentage changes in TG and high-sensitivity C-reactive protein (hsCRP) from baseline (i.e. start of the open-label extension after 12 weeks of treatment with rosuvastatin 10mg + fenofibric acid 135 mg) to incremental time points up to 52 weeks in the extension study, and the proportion of patients achieving individual and combined goals for LDL-C and non-HDL-C. Adverse events (AEs) and clinical laboratory values were also assessed. Results: Of the 261 patients initially randomized to rosuvastatin 10mg + fenofibric acid 135 mg, 220 completed the controlled study and 187 continued treatment with rosuvastatin 20mg + fenofibric acid 135mg in the extension study. Increasing the rosuvastatin dose from 10mg to 20mg in combination with fenofibric acid 135mg for up to 52 weeks resulted in significant (p ≤ 0.005 for all comparisons) mean percentage changes from baseline in LDL-C (--9.5%), non-HDL-C (--6.0%), ApoB (--8.5%), and HDL-C (3.6%), while median TG levels remained largely unchanged (0.8%, p = 0.055) at the week 52 visit. Greater percentages of patients achieved their risk-stratified lipid goals at week 52 compared with baseline for LDL-C (89% vs 84%), non-HDL-C (50% vs 25%), and both LDL-C and non-HDL-C (50% vs 19%). Combination therapy was generally well tolerated. The incidence of muscle-, hepatic-, and renal-related AEs and laboratory values were within the expected range. Conclusion: This study demonstrates that 1-year therapy with rosuvastatin + fenofibric acid is well tolerated and that increasing the rosuvastatin dose from 10mg to 20 mg in the combination results in additional beneficial effects on key lipid parameters in patients with mixed dyslipidemia. [ABSTRACT FROM AUTHOR]

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]

Background: Patients with chronic kidney disease (CKD) often have mixed dyslipidemia and high cardiovascular disease risk. Although statins reduce LDL-C, adding a fibrate may further improve lipid parameters. Objective: This multicenter, randomized study evaluated the short-term efficacy and safety profile of fenofibric acid (FA) + rosuvastatin (R) combination therapy for improving lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. The study also assessed estimated glomerular filtration rate after study drug washout. Methods: Patients received FA 45 mg + R (5 mg for 8 weeks, then 10 mg for 8 additional weeks) or R monotherapy (5 mg for 8 weeks, then 10 mg for 8 additional weeks), followed by an 8-week washout period. Primary and secondary end points were percent changes in triglycerides and HDL-C, respec-tively, from baseline to week 8. Results: FA 45 mg + R 5 mg, compared with R 5 mg, resulted in significant improvements in triglycer- ides (median % changes: week 8, -38.0% vs -22.4%, P < 0.001; week 16, -42.6% vs -29.7%, P < 0.001) and HDL-C (mean % changes: week 8, 16.9% vs 7.8%, P < 0.001; week 16, 17.3% vs 8.9%, P < 0.001). Adverse event rates were similar between groups (70.7% with FA + R vs 68.6% with R). Mean serum creatinine level at baseline was 1.36 mg/dL in the FA + R group and 1.38 mg/dL in the R group. The final treatment serum creatinine value, defined as the last nonmissing postbaseline value collected within 30 days after the last dose of study drug, was 1.52 mg/ dL with FA + R (vs 1.41 mg/dL with R; P < 0.001), which then decreased to 1.39 mg/dL after the 8-week washout (vs 1.42 mg/dL with R). Conclusions: The data suggest that, after 16 weeks of therapy, FA + R has an acceptable safety profile and improved TG and HDL-C efficacy versus R. FA + R combination therapy may thus further improve lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. ClinicalTrials.gov identifier: NCT00680017. [ABSTRACT FROM AUTHOR]