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 regular and extended-release gemfibrozil on plasma lipoprotein and apolipoprotein (apo) levels in hypercholesterolemic subjects with decreased high density lipoprotein (HDL) cholesterol (C) levels. Study participants were men and women 19 to 80 years of age with baseline plasma low density lipoprotein (LDL) C levels > or = 4.5 mmol/l (175 mg/dl), HDL-C levels < or = 1.2 mmol/l (45 mg/dl), and triglyceride levels < or = 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) for 3 months (placebo trial). In the second protocol 655 subjects were randomized to regular or extended-release gemfibrozil (1200 mg/day) for 6 months (equivalency trial). Changes in lipids and apos were stratified by baseline HDL-C levels (< 0.9 mmol/l, and 0.9-12.2 mmol/l). In both studies, treatment with gemfibrozil, either regular or extended-release, 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 measured LDL-C levels were observed in both groups (3-6% and 8-9%, respectively). These reductions were less than those observed for calculated LDL-C (7-10% and 11%, respectively). For apo B, reductions were 11-14% and 16-17% in the two groups. HDL-C, apo A-I, and apo A-II levels increased 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 reached statistical significance in the equivalency trial (P < 0.0001) and were independent of baseline triglyceride levels. Our data indicate that 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 levels (< 0.9 mmol/l). Moreover, this agent lowers VLDL-C somewhat more than triglyceride, resulting in an underestimation of calculated VLDL-C reductions and in an overestimation of calculated LDL-C reductions. This agent also raises apo A-II levels much more than apo A-I levels.
Schaefer
E J
EJ
Division of Endocrinology, Metabolism, and Molecular Biology, Lipid Research Laboratory, New England Medical Center, Boston, MA, USA.
Lamon-Fava
S
S
Cole
T
T
Sprecher
D L
DL
Cilla
D D
DD
Balagtas
C C
CC
Rowan
J P
JP
Black
D M
DM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001053:Apolipoproteins / Q000097:blood* / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D015243:Cholesterol, VLDL / Q000097:blood / Q000187:drug effects; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015248:Gemfibrozil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; D015248:Gemfibrozil