Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state

A randomized, double-blind, placebo-controlled study was undertaken in 20 h ypertriglyceridemic men [plasma triglyceride (TG), >2.3 mM] with low levels (<0.9 mM) of high-density lipoprotein cholesterol (HDL-C) to investigate t he ability of micronized fenofibrate (Tricor or Lipidil; 200 mg/ day) to af fect atherogenic and thrombogenic plasma risk factors in the fed and fasted state. Each patient underwent (a) 4 weeks of dietary stabilization, (b) 8 weeks of treatment with fenofibrate or placebo, (c) a 5-week washout period , and (d) 8-weeks of treatment with the alternative medication. An oral fat -loading test (1 g fat/kg body weight) was carried out after both treatment periods. Before treatment, patients had a mean (+/-SD) total plasma TG of 3.31 +/- 0.93 mM; total C, 5.75 +/- 0.89 mM; HDL-C, 0.71 +/- 0.09 mM; and l ow-density lipoprotein (LDL)C, 3.40 +/- 0.68 mM. Compared with placebo, fen ofibrate reduced fasting TG levels by 36%, and triglyceride-rich lipoprotei n (TRL, d < 1.006 g/ml) -TG, and TRL-C levels by similar to 40%. In the pos tprandial state, fenofibrate reduced total TG, TRL-TG, TRL-C, TRL-apoC-III, and TRL-apoE levels by similar to 35% (all values of p < 0.01). Fasted and fed HDL-C and apoA-I levels were increased similar to 10%, and total chole sterol/HDL cholesterol ratios were decreased similar to 15% by fenofibrate. No significant differences were observed in mean LDL-C and LDL-apoB levels . A 6% increase in the LDL-C/LDL-apoB ratio during fenofibrate treatment in dicated a shift to larger, more buoyant LDL par tides. A small, but statist ically significant (p < 0.01) increase was observed in fasted and fed Lp(a) levels during fenofibrate treatment. Hemostatic parameters were not signif icantly affected by fenofibrate, except for a 12-15% decrease (p < 0.05) in fibrinogen levels in the fasted and fed state, and a significant increase (43%; p < 0.05) in fasting levels of plasminogen activator-inhibitor-1. The se data demonstrate that micronized fenofibrate is highly effective, in bot h the fed and fasted state, in reducing TRL lipids and apolipoproteins, and in reducing plasma fibrinogen levels of men with an atherogenic lipoprotei n profile.