The long-term effects of niceritrol on lipoprotein(a) (Lp[a]), lipids, apolipoproteins, and fibrinogen and fibrinolytic factors were evaluated in 20 outpatients who had serum Lp(a) levels higher than 20 mg/dL. The mean ( +/- SE) levels of Lp(a) decreased from 33.6 +/- 2.3 mg/dL to 23.5 +/- 3.5 mg/dL after 12 months of niceritrol treatment (P < 0.01). Serum levels of triglycerides and apolipoprotein E decreased significantly and high-density lipoprotein cholesterol (HDL-C) increased significantly after 12 months (P < 0.05). There were no significant changes overall in fibrinogen and fibrinolytic factors, although fibrinogen concentrations showed a tendency to decrease with treatment. PAI-1 levels decreased significantly (P < 0.05) after 6 months of niceritrol treatment. A significant correlation of percent reduction between Lp(a) and apolipoprotein B levels (P < 0.01) was observed, suggesting that the Lp(a)-lowering effects of niceritrol may be due to niceritrol inhibition of apolipoprotein B synthesis, the major apolipoprotein of Lp(a). The ability of niceritrol to decrease Lp(a) levels and increase HDL-C levels, together with its tendency to lower fibrinogen levels, may help prevent coronary events in patients with high levels of Lp(a).