Long-Term Effects of Fenofibric Acid + Statin Combination Therapy in Patients with High Triglycerides and Low HDL-C †

Abstract

Synopsis: Three 12-week controlled studies demonstrated the efficacy and safety of combination therapy with fenofibric acid (FA) + statins in patients with mixed dyslipidemia defined as high triglycerides (TG $150 mg/dL), low highdensity lipoprotein cholesterol (HDL-C; men/women ,40/ ,50 mg/dL), and elevated low-density lipoprotein cholesterol (LDL-C; $130 mg/dL). A subsequent 52-week, openlabel extension study evaluated the long-term safety and efficacy of FA 135 mg + moderate-dose statin (MDS; rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg). Purpose: To evaluate the long-term efficacy of combination therapy with FA + MDS in patients initially treated for 12 weeks with statin monotherapy. Methods: This prespecified analysis included the subset of patients who completed 12 weeks of treatment with statin monotherapy (rosuvastatin 10, 20, or 40 mg; simvastatin 20, 40, or 80 mg; or atorvastatin 20, 40, or 80 mg) in 1 of 3 controlled studies and subsequently received $1 dose of FA + MDS in the open-label extension study. Baseline was defined as the last value prior to the first dose of FA + MDS in the extension study. Mean or median percent changes from baseline in efficacy parameters were determined. Results: The mean age of patients in this analysis (n 5 893) was 55 years; 49% were women, 94% were white, and 21% had type 2 diabetes. At baseline of the extension study (after 12 weeks of statin monotherapy), mean HDL-C, TG, and LDL-C were 41.2 mg/dL, 199.2 mg/dL, and 94.4 mg/dL, respectively. Switching to combination therapy with FA + MDS for 52 weeks resulted in a mean percent increase in HDL-C (14.1%) and a mean percent decrease in TG (–25.4%; Figure). Non-HDL-C, apolipoprotein B (ApoB), VLDL-C, high-sensitivity C-reactive protein, and total-C were also improved after 52 weeks of combination therapy. Although modest mean percent increases in LDL-Cwere observed in the first 12 weeks of combination therapy, the increases gradually became smaller over time. After 52 weeks of therapy, mean LDL-C was 91.9 mg/dL, remaining at less than recommended levels for high-risk patients. Combination therapy was generallywell tolerated and no case of rhabdomyolysiswas reported. Conclusions: In patients with high TG and low HDL-C initially treated with statin monotherapy, long-term treatment with FA + MDS resulted in incremental and sustained.