Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study

Abstract

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone.Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes.Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy.Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

Effect of fenofibrate in 1113 patients at low-density lipoprotein cholesterol goal but high triglyceride levels: Real-world results and factors associated with triglyceride reduction

“…The median change in TG in our study was -60% and is relatively greater than those of prior reports. A few recent studies performed in Asia and the United States showed percentage change ranging from -36% to -43% [ 11 , 13 , 14 ]. Of note, a study performed in our group revealed TG reduction down to -53% [ 1 ].…”

“…Fibrate therapy has been known to change TG levels by around -40% in clinical trials [ 11 – 14 ]. However, the efficacy of lipid-lowering agents can be varied to some degree according to individual’s characteristics [ 15 ].…”

Fenofibrate prevents iron induced activation of canonical Wnt/β-catenin and oxidative stress signaling in the retina

“…Further, our ICP-MS and Ferrozine iron chelation assay strongly demonstrated that fenofibrate treated cells have significantly lower levels of intracellular iron by chelating it. Although we found only one clinical report on fenofibrate inducing anemia 67 , interestingly, the EFECTL Study (Effect of Fenofibrate and Ezetimibe Combination Treatment on Lipid Study), a three-arm parallel-group open-label randomized trial, reported that 52 patients undergoing fenofibrate monotherapy alone had a significant reduction in the red blood cell count and hemoglobin starting from 4 weeks after treatment was initiated until 52 weeks for the entire duration of the study 68 . Our present finding that fenofibrate is an iron chelator provides a plausible explanation for the results seen in EFECTL trial.…”

The Combination Therapy of Fenofibrate and Ezetimibe Improved Lipid Profile and Vascular Function Compared with Statins in Patients with Type 2 Diabetes

“…Oikawa et al reported that the combination therapy with fenofibrate and ezetimibe reduces concentrations of LDL-cholesterol and triglyceride and is safe in a long-term treatment 17 ) . We found that the treatment with the combination significantly reduced the cholesterol levels in small and very small fractions of LDL and increased the cholesterol levels in large fractions of LDL.…”