“The main intent of the study was to evaluate the benefit of adding a fibrate such as fenofibric acid to a very efficacious LDL-C reducing combination such as atorvastatin + ezetimibe in people who have high TG (triglycerides) and low HDL-C in addition to high LDL-C,” explained Dr. Peter H. Jones via email.
“These types of mixed-dyslipidemia folks frequently have insulin resistance, such as with metabolic syndrome and type 2 diabetes, and are at high risk for cardiovascular disease,” he continued. “Their lipid goals are not just LDL-C but also measures of particle number such as non-HDL-C and apo B.”
Dr. Jones, at Baylor College of Medicine, Houston, Texas and colleagues conducted a phase III trial involving 543 patients with triglyceride levels of at least 150 mg/dL but less than 400 mg/dL, HDL cholesterol less than 40 mg/dL for men or 50 mg/dL for women, and LDL cholesterol of 130 mg/dL or more. They were treated for 12 weeks with atorvastatin 40 mg plus ezetimibe 10 mg with or without fenofibric acid 135 mg.
Of the original group, 486 completed the trial. HDL-C levels increased by 13.0% in the fenofibric acid group compared to 4.2% in the group receiving atorvastatin + ezetimibe only (p<0.001), the team found.
The mean change in triglycerides in the two groups was -57.3% and -39.7%, respectively (p<0.001), according to the report. The drop in LDL-C was similar in both arms, -52.9% vs -52.0%
“Fenofibric acid + atorvastatin/ezetimibe resulted in a significantly greater effect on all secondary variables of non-HDL-C, ApoB, ApoAI, VLDL-C, ApoCIII, and hsCRP versus atorvastatin/ezetimibe,” Dr. Jones and colleagues report.
More patients in the fenofibric acid group attained treatment goals; for example, 88.4% vs 80.8% achieved the combined target of LDL-C <100 mg/dL, non-HDL-C <130 mg/dL, and ApoB <90 mg/dL.
The researchers report that both regimens were generally well tolerated. Are there any contraindications to using fenofibric acid? “The only caution for use of fenofibric acid is to avoid it with eGFR (estimated glomerular filtration rate) < 30, and to use a lower dose if eGFR is 30-50,” Dr. Jones advised.
Summing up the findings, he concluded: “”We showed that the addition of fenofibric acid increased HDL-C and reduced non-HDL-C and apo B more than atorvastatin + ezetimibe. As a result, the number of these people who attained the most intensive goals for LDL-C, non-HDL-C and apo B combined were numerically higher with the 3 drugs.”
Efficacy and safety of fenofibric acid in combination with atorvastatin and ezetimibe in patients with mixed dyslipidemia
Am Heart J 2010;160:759-766.