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 HYPERLIPIDEMIA AND CORONARY-ARTERY DISEASE

Background Hypolipidaemic agents do not usually normalize all of the m ultiple lipoprotein abnormalities in patients with familia[ combined h yperlipidaemia (FCHL). The effect of the simvastatin-ciprofibrate comb ination in comparison with each drug alone on the lipoprotein abnormal ity patterns was studied in patients with FCHL and coronary artery dis ease (CAD). Methods Sixty patients (53 men and seven women), mean age 52 years (range 36-60 years), were studied. After a 4-week placebo per iod, 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 combinat ion of both drugs for a 12-week period, Parameters measured were as fo llows: plasma fibrinogen, total cholesterol, triglycerides, low densit y lipoprotein (LDL), very low density lipoprotein, intermediate densit y lipoprotein, and high density lipoprotein cholesterol, as well as LD L subfraction distribution and structure by density gradient ultracent rifugation. Apoproteins (ape) B and Al were assessed by immunoturbidom etry. Results At baseline, apoB, LDL cholesterol and triglycerides wer e increased, whereas LDL particles were small and dense. ApoB was sign ificantly reduced by all three interventions. Drug combination and cip rofibrate significantly reduced plasma fibrinogen (-24 and -25%, respe ctively; P < 0.001) and triglycerides (-51 and -49%, respectively; P < 0.001). Drug combination and simvastatin significantly reduced LDL ch olesterol (-25 and -22%, respectively; P < 0.001) compared with ciprof ibrate (-10%; P < 0.01). Ciprofibrate and drug combination increased L DL particle size (parameter K -0.24 versus -0.61 and -0.30 versus -0.6 2, respectively; P < 0.001), whereas simvastatin had no significant ef fect on LDL particle size. The cholesterol content of LDL particles wa s reduced with ciprofibrate and the drug combination only in the dense LDL particles (LDL(3-5)) and increased in the light (LDL(1-2)) subfra ctions, whereas simvastatin reduced the cholesterol content of all LDL subfractions except LDL(2). Ciprofibrate and drug combination reduced the triglyceride content of all LDL subfractions. Conclusion Combined treatment with simvastatin and ciprofibrate effectively reduced plasm a fibrinogen, triglycerides, total and LDL cholesterol and increased L DL particle size in patients with FCHL and CAD. These effects might in duce a clinical benefit for these patients.