A retrospective meta-analysis of the efficacy and tolerability of Fenofibrate 300 mg/d on high-density lipoprotein cholesterol levels in randomized, double-blind, comparative studies conducted in Japan

Background: Low levels of plasma high-density lipoprotein cholesterol (HDL-C) represent an important risk factor for coronary heart disease (CHD). Increasing HDL-C by 1 mg/dL decreases the incidence of CHD by 2% to 3%. Fenofibrate increases HDL-C by similar to23%, to greater than or equal to40 mg/dL, and may be effective in preventing CHD. Objective: The aim of this study was to assess the effects of fenofibrate on HDL-C in patients treated for 12 weeks in 3 randomized, double-blind, comparative studies conducted in Japan. Changes in total cholesterol (TC) and triglycerides (TG), effects on HDL-C and apolipoprotein (apo) A-I and A-II by TG level, and effects on serum lipid levels by type of hyperlipidemia were the secondary end points. Methods: Changes in HDL-C levels, as well as TC and TG levels, were analyzed in patients who received fenofibrate 300 mg/d for 12 weeks. Patients aged 20 to 80 years with mean TC greater than or equal to220 mg/dL (hypercholesterolemia), TG greater than or equal to150 mg/dL (hypertriglyceridemia), or both (combined hyperlipidemia) were considered assessable. Results: In this retrospective meta-analysis conducted at Grelan Pharmaceutical Co. Ltd. (Tokyo, Japan), data from 263 patients (137 women, 126 men; mean [SD] age, 56.0 [10.8] years; range, 25-79 years) were included. The mean (SD) HDL-C level increased significantly, from 46.1 (0.9) mg/dL to 55.9 (1.0) mg/dL after 12 weeks of treatment with fenofibrate (P < 0.001). Serum TC and TG decreased significantly (both P < 0.001). HDL-C elevation was greater in patients with TG greater than or equal to150 mg/dL than in patients with TG < 150 mg/dL, although apo A-I and A-II changes were the same in both groups. HDL-C increased in every type of hyperlipidemia, 14.9% in hypercholesterolemia, 22.0% in hypertriglyceridemia, and 33.5% in combined hyperlipidemia. Baseline HDL-C levels were <40 mg/dL in 93 patients (group 1) and greater than or equal to40 mg/dL in 170 patients (group 2). Mean HDL-C levels increased significantly in both groups during the treatment period, from 32.6 (0.6) mg/dL to 42.6 (1.0) mg/dL in group I and from 53.5 (0.9) mg/dL to 63.1 (1.1) mg/dL in group 2 (both P < 0.001). One patient (0.3%) of the 331 included in the tolerability analysis experienced a serious adverse effect (jaundice). Conclusion: In this study of patients with hypercholesterolemia, hypertriglyceridemia, or combined hyperlipidemia, 12-week treatment with fenofibrate 300 mg/d was effective and generally well tolerated, with the possible exception of transient changes in aminotransferases. HDL-C was increased in all patients to ∼40 mg/dL, the target level.