EFFECTS OF REGULAR AND EXTENDED-RELEASE GEMFIBROZIL ON PLASMA-LIPOPROTEINS AND APOLIPOPROTEINS IN HYPERCHOLESTEROLEMIC PATIENTS WITH DECREASED HDL CHOLESTEROL LEVELS

We have studied, in a prospective blinded fashion, the effects of regu lar and extended-release gemfibrozil on plasma lipoprotein and apolipo protein (apo) levels in hypercholesterolemic subjects with decreased h igh density lipoprotein (HDL) cholesterol (C) levels. Study participan ts were men and women 19 to 80 years of age with baseline plasma low d ensity lipoprotein (LDL) C levers greater than or equal to 4.5 mmol/l (175 mg/dl), HDL-C levels less than or equal to 1.2 mmol/l (45 mg/dl), and triglyceride levels less than or equal to 3.4 mmol/L (300 mg/dl). All subjects were stabilized on a diet for eight weeks prior to entry into two different protocols. In the first protocol 229 subjects were randomized to placebo or extended-release gemfibrozil (1200 mg/day) f or 3 months (placebo trial). In the second protocol 655 subjects were randomized to regular or extended-release gemfibrozil (1200 mg/day) fo r 6 months (equivalency trial). Changes in lipids and apos were strati fied by baseline HDL-C levels (< 0.9 mmol/l, and 0.9-1.2 mmol/l). In b oth studies, treatment with gemfibrozil, either regular or extended-re lease, was associated with significant (P < 0.05) decreases in plasma very low density lipoprotein (VLDL) C and triglyceride levels of 42-45 % and 33-37%, respectively, in subjects with HDL-C level < 0.9 mmol/l, and of 38-47% and 32-39%, respectively, in patients with HDL-C levels of 0.9-1.2 mmol/l. Modest reductions from baseline in directly measur ed LDL-C levels were observed in both groups (3-6% and 8-9%, respectiv ely). These reductions were less than those observed for calculated LD L-C (7-10% and 11%, respectively). For apo B, reductions were 11-14% a nd 16-17% in the two groups. HDL-C, apo A-I, and apo A-II levels incre ased by 15-16%, 5-6%, and 21-25%, respectively, in patients with HDL-C <0.9 mmol/l, and by 6-7%, 2-3%, and 19-22%, respectively, in patients with HDL-C of 0.9-1.2 mmol/l. These differences in HDL-C levels reache d statistical significance in the equivalency trial (P < 0.0001) and w ere independent of baseline triglyceride levels. Our data indicate tha t gemfibrozil, either regular or extended-release, is highly effective in lowering plasma triglyceride levels and increases HDL-C levels by approximately 15% in hypercholesterolemic patients with low HDL-C leve ls (< 0.9 mmol/l). Moreover, this agent lowers VLDL-C somewhat more th an triglycerides, resulting in an underestimation of calculated VLDL-C reductions and in an overestimation of calculated LDL-C reductions. T his agent also raises apo A-II levels much more than apo A-I levels.