One-year efficacy and safety of rosuvastatin + fenofibric acid combination therapy in patients with mixed dyslipidemia: evaluation of dose response.

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 10 mg + fenofibric acid 135 mg 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 20 mg + 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 20 mg + fenofibric acid 135 mg. The present post hoc analysis evaluated patients who were treated with rosuvastatin 10 mg + fenofibric acid 135 mg in the controlled study and received rosuvastatin 20 mg + fenofibric acid 135 mg 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 ≥150 mg/dL, LDL-C ≥130 mg/dL, and HDL-C <40/50 mg/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), and median 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 10 mg + 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 10 mg + fenofibric acid 135 mg, 220 completed the controlled study and 187 continued treatment with rosuvastatin 20 mg + fenofibric acid 135 mg in the extension study. Increasing the rosuvastatin dose from 10 mg to 20 mg in combination with fenofibric acid 135 mg 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 10 mg to 20 mg in the combination results in additional beneficial effects on key lipid parameters in patients with mixed dyslipidemia. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifiers NCT00300482 and NCT00300430.