Post-prandial effects of gemfibrozil vs simvastatin in hypercholesterolemic subjects with borderline hypertriglyceridemia.
OBJECTIVE
Impaired triglyceride-rich lipoprotein metabolism is most probably related to an enhanced cardiovascular risk, and may be associated with a pro-coagulant state. A double-blind, randomized study was undertaken to evaluate two widely utilized hypolipidemic drugs in the post-prandial phase and their impact on lipid, coagulation and fibrinolytic parameters.


RESULTS
Thirty middle-aged men selected according to their low density lipoprotein-cholesterol (LDL-C) > or = 160 and < or = 240 mg/dl and borderline hypertriglyceridemia (110-220 mg/dl) after at least one month of a lipid-lowering diet received gemfibrozil (600 mg bid) or simvastatin (20 mg qd) and the corresponding placebo. On enrollment and after 2 months of drug treatment, they were tested with a standard oral fat load (OFL) (35 g fat/m2 body surface). On both occasions plasma total-cholesterol, LDL-C, HDL-C, triglycerides, lipoprotein[a] (Lp[a]), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), antithrombin-III (AT-III), plasminogen and fibrinogen were determined just before the meal (t0) and at times 2 hours, 4 h, 6 h, 8 h after it (t2-t8). A two-factor (time and visit) multivariate analysis for repeated measurements was performed to evaluate the data. Total cholesterol, and LDL-C were significantly diminished 2 months after both gemfibrozil and simvastatin, the latter being more active. Plasma triglycerides showed a marked reduction with gemfibrozil at all times, while simvastatin regimen yielded only minor modifications. HDL-C was only slightly increased by simvastatin; Lp[a] plasma levels were almost unaffected. Small fibrinogen (t0, t2, t6, t8), PAI-1 (t6) and AT III (t0-t8) increases were observed after gemfibrozil, while simvastatin did not significantly modify these parameters.


CONCLUSIONS
In the post-prandial phase, gemfibrozil and simvastatin induce different metabolic effects that beneficially influence the lipid pattern, whereas fibrinolytic and coagulative parameters display minor variations of undetermined significance.
Vigna
G B
GB
Institute of Internal Medicine, University of Trieste, Italy.
Donega
P
P
Passaro
A
A
Zanca
R
R
Cattin
L
L
Fonda
M
M
Pauciullo
P
P
Marotta
G
G
Fellin
R
R
Gasparrini
S
S
Piliego
T
T
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001777:Blood Coagulation / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D015248:Gemfibrozil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007558:Italy; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019518:Postprandial Period; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D019821:Simvastatin; D015248:Gemfibrozil