Effects of simvastatin and ciprofibrate alone and in combination on lipid profile, plasma fibrinogen and low density lipoprotein particle structure and distribution in patients with familial combined hyperlipidaemia and coronary artery disease.
BACKGROUND
Hypolipidaemic agents do not usually normalize all of the multiple lipoprotein abnormalities in patients with familial combined hyperlipidaemia (FCHL). The effect of the simvastatin-ciprofibrate combination in comparison with each drug alone on the lipoprotein abnormality patterns was studied in patients with FCHL and coronary artery disease (CAD).


METHODS
Sixty patients (53 men and seven women), mean age 52 years (range 36-60 years), were studied. After a 4-week placebo period, patients were randomly assigned to three groups. The first group (n = 20) received simvastatin (20 mg daily), the second group (n = 20) ciprofibrate (100 mg daily) and the third group (n = 20) the combination of both drugs for a 12-week period. Parameters measured were as follows: plasma fibrinogen, total cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein, intermediate density lipoprotein, and high density lipoprotein cholesterol, as well as LDL subfraction distribution and structure by density gradient ultracentrifugation. Apoproteins (apo) B and AI were assessed by immunoturbidometry.


RESULTS
At baseline, apoB, LDL cholesterol and triglycerides were increased, whereas LDL particles were small and dense. ApoB was significantly reduced by all three interventions. Drug combination and ciprofibrate significantly reduced plasma fibrinogen (-24 and -25%, respectively; P < 0.001) and triglycerides (-51 and -49%, respectively; P < 0.001). Drug combination and simvastatin significantly reduced LDL cholesterol (-25 and -22%, respectively; P < 0.001) compared with ciprofibrate (-10%; P < 0.01). Ciprofibrate and drug combination increased LDL particle size (parameter K -0.24 versus -0.61 and -0.30 versus -0.62, respectively; P < 0.001), whereas simvastatin had no significant effect on LDL particle size. The cholesterol content of LDL particles was reduced with ciprofibrate and the drug combination only in the dense LDL particles (LDL3-5) and increased in the light (LDL1-2) subfractions, whereas simvastatin reduced the cholesterol content of all LDL subfractions except LDL2. Ciprofibrate and drug combination reduced the triglyceride content of all LDL subfractions.


CONCLUSIONS
Combined treatment with simvastatin and ciprofibrate effectively reduced plasma fibrinogen, triglycerides, total and LDL cholesterol and increased LDL particle size in patients with FCHL and CAD. These effects might induce a clinical benefit for these patients.
Kontopoulos
A G
AG
Division of Cardiology, Aristotelian University, Thessaloniki, Greece.
Athyros
V G
VG
Papageorgiou
A A
AA
Hatzikonstandinou
H A
HA
Mayroudi
M C
MC
Boudoulas
H
H
D000328:Adult; D000704:Analysis of Variance; D002995:Clofibric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D058607:Fibric Acids; D005340:Fibrinogen / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011446:Prospective Studies; D012449:Safety; D019821:Simvastatin; D015996:Survival Rate; D016896:Treatment Outcome; D014461:Ultracentrifugation
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D008055:Lipids; D008077:Lipoproteins, LDL; D002995:Clofibric Acid; D005340:Fibrinogen; D008148:Lovastatin; D019821:Simvastatin; C019304:ciprofibrate