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Background: Patients with mixed dyslipidemia often require combination therapy to manage multiple lipid abnormalities. Objective: To evaluate fenofibric acid in combination with a statin across three studies of patients with mixed dyslipidemia. Methods: As prospectively planned, data were pooled from three randomized, double-blind, phase 3 studies of patients with low-density lipoprotein cholesterol (LDL-C) ≥130mg/dL, triglycerides (TG) ≥150mg/dL, and high-density lipoprotein cholesterol (HDL-C) <40mg/dL (men) or <50mg/dL (women). A total of 2715 patients were randomly assigned to 12-week treatment with fenofibric acid 135mg monotherapy; low-, moderate-, or high-dose statin (rosuvastatin, simvastatin, or atorvastatin, depending on study) monotherapy; or fenofibric acid + low- or moderate-dose statin. The primary efficacy comparisons were mean percent change in HDL-C and TG (combination therapy vs. statin) and LDL-C (combination therapy vs. fenofibric acid). Results: Fenofibric acid + low-dose statin increased HDL-C (18.1% vs. 7.4%) and reduced TG (−43.9% vs. −16.8%) versus low-dose statin monotherapy and reduced LDL-C (−33.1% vs. −5.1%) versus fenofibric acid monotherapy (P <.001 for all). Fenofibric acid + moderate-dose statin increased HDL-C (17.5% vs. 8.7%) and reduced TG (−42.0% vs. −23.7%) versus moderate-dose statin monotherapy and reduced LDL-C (−34.6% vs. −5.1%) versus fenofibric acid monotherapy (P <.001 for all). Combination therapy was generally well tolerated, and safety profiles were similar to monotherapies. No rhabdomyolysis was reported. Conclusion: In patients with mixed dyslipidemia, combination therapy simultaneously improved multiple lipid abnormalities more effectively than fenofibric acid or statin monotherapies. [Copyright &y& Elsevier]

Background: Co-administration of a fibrate and statin is an effective treatment option for patients with multiple lipid abnormalities, yet adequate long-term safety and efficacy data are lacking. Objective: To evaluate the long-term safety and efficacy of fenofibric acid combined with statins in adults with mixed dyslipidemia. Methods: Three large, 12-week, phase three, double-blind, randomized, controlled trials evaluated fenofibric acid 135 mg combined with a low- or moderate-dose statin compared to fenofibric acid or statin monotherapy, and a subsequent 52-week open-label extension study evaluated fenofibric acid 135 mg combined with moderate-dose statin (rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg). This prespecified analysis integrated results from these studies to assess the long-term safety and efficacy of combination therapy. Results: Across the controlled studies and the extension study, 2201 patients received at least one dose of fenofibric acid + statin for a median duration of 364 days. The most common adverse events were headache, upper respiratory tract infection, nasopharyngitis, and back pain, with the incidence of all adverse events being similar across all combination therapy treatment groups. Rhabdomyolysis or treatment-related death was not reported in any group. Combination therapy resulted in sustained improvements in multiple lipid parameters, including triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Conclusion: Long-term fenofibric acid + statin combination therapy was generally well tolerated and resulted in comprehensive and sustained improvements in multiple lipid parameters in adults with mixed dyslipidemia. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate a new formulation of fenofibric acid (ABT-335) co-administered with 2 doses of rosuvastatin in patients with mixed dyslipidemia. Methods: In a phase 3, multicenter, randomized, double-blind, active-controlled study, a total of 1445 patients with LDL-C≥130mg/dL, TG≥150mg/dL, and HDL-C<40mg/dL (<50mg/dL for women) were randomized to either ABT-335 (135mg), rosuvastatin (10, 20, or 40mg), or ABT-335+rosuvastatin 10 or 20mg, and treated for 12 weeks. The primary efficacy comparisons were mean percent change in HDL-C and TG (ABT-335+rosuvastatin vs. corresponding dose of rosuvastatin), and LDL-C (ABT-335+rosuvastatin vs. ABT-335). Results: Combination therapy with ABT-335+rosuvastatin 10mg resulted in significantly (p <0.001) greater improvements in HDL-C (20.3% vs. 8.5%) and TG (−47.1% vs. −24.4%) compared to rosuvastatin 10mg; and LDL-C (−37.2% vs. −6.5%) compared to ABT-335. Similarly, significantly (p <0.001) greater improvements were observed with ABT-335+rosuvastatin 20mg in HDL-C (19.0% vs. 10.3%) and TG (−42.9% vs. −25.6%) compared to rosuvastatin 20mg; and LDL-C (−38.8% vs. −6.5%) compared to ABT-335 monotherapy. Greater improvements in multiple secondary endpoints were noted with combination therapy compared to prespecified monotherapies. Both combination therapy doses were generally well tolerated, with a safety profile consistent with ABT-335 and rosuvastatin monotherapies. No rhabdomyolysis or unexpected hepatic, renal, or muscle safety signals were identified. Conclusion: In patients with mixed dyslipidemia, combination therapy with ABT-335+rosuvastatin resulted in more effective control of multiple lipid parameters than either monotherapy alone, with a safety profile similar to both monotherapies. This combination may be an appropriate therapeutic option to treat mixed dyslipidemia. [Copyright &y& Elsevier]