Efficacy and safety of ABT-335 (fenofibric acid) in combination with simvastatin in patients with mixed dyslipidemia: A phase 3, randomized, controlled study

BackgroundPatients with mixed dyslipidemia often require combination therapy to effectively control lipid abnormalities. This study compared the effects of combination therapy with ABT-335 (a new formulation of fenofibric acid) and simvastatin to ABT-335 and simvastatin monotherapies on lipid and nonlipid parameters in patients with mixed dyslipidemia.MethodsThis was a phase 3, multicenter, randomized, double-blind, active-controlled study. A total of 657 patients with mixed dyslipidemia (low-density lipoprotein cholesterol [LDL-C] ≥130 mg/dL, triglycerides [TGs] ≥150 mg/dL, and high-density lipoprotein cholesterol [HDL-C]<40 mg/dL [men] or <50 mg/dL [women]) were randomized to 12 weeks of treatment with ABT-335 + simvastatin (20 or 40 mg) combination therapy, ABT-335 monotherapy (135 mg), or simvastatin monotherapy (20, 40, or 80 mg).ResultsCombination therapy resulted in significantly greater increases in HDL-C and decreases in TGs compared to the corresponding simvastatin monotherapy dose (P < .001) and decreases in LDL-C compared to ABT-335 monotherapy (P < .001). HDL-C increased 17.8% versus 7.2% and TGs decreased −37.4% versus −14.2% (ABT-335 + simvastatin 20 vs simvastatin 20); LDL-C decreased −24.0% versus −4.0% (ABT-335 + simvastatin 20 vs ABT-335). HDL-C increased 18.9% versus 8.5% and TGs decreased −42.7% versus −22.4% (ABT-335 + simvastatin 40 vs simvastatin 40); LDL-C decreased −25.3% versus −4.0% (ABT-335 + simvastatin 40 vs ABT-335). Twelve-week treatment with combination therapy was generally well tolerated with a safety profile consistent with ABT-335 and simvastatin monotherapies. No cases of rhabdomyolysis were reported.ConclusionFor patients with mixed dyslipidemia, combination therapy provided more effective control of multiple lipid parameters than either monotherapy alone, with a safety profile similar to both monotherapies.