Ciprofibrate increases plasma concentration of platelet-derived growth factor AB in patients with advanced atherosclerosis and hyperlipidemia independently of its hypolipidemic effects.

Fibrates, besides their hypolipidemic action, share alternative effects, such as decreased plasma fibrinogen and uric acid levels. Because of their complex action, additional effects have been investigated. A group of 23 patients with clinical signs of atherosclerosis and hyperlipoproteinemia was randomly allocated after a 1-month washout period and treated with either 100 mg/d of ciprofibrate or 100 mg/d of aspirin for 2 months. Patients were then treated with a combination of these two agents for the next 2 months. Ciprofibrate decreased plasma concentrations of triglycerides (-29%) and very-low-density lipoprotein cholesterol (-27%) in monotherapy and a larger reduction was observed if ciprofibrate was added to the aspirin therapy: triglycerides (-39%), very-low-density lipoprotein cholesterol (-33%), total cholesterol (-18%), low-density lipoprotein cholesterol (-17%), and increased high-density lipoprotein cholesterol (+36%). Ciprofibrate increased plasma levels of platelet-derived growth factor (PDGF) AB in both monotherapy patients (+162.9 pg/ml, +297%) and in aspirin-pretreated patients (+129.8 pg/ml, +134%); the increase of PDGF AB platelet store was significant only in aspirin-pretreated patients (+11.1 ng/ml, +51%). Aspirin in monotherapy did not modulate either plasma or platelet store of PDGF AB. Ciprofibrate did not inhibit thromboxane B 2 synthesis in platelets. Aspirin did not influence plasma thromboxane B 2 concentration at all, whereas it decreased thromboxane B 2 platelet production markedly in monotherapy (-85%) and in combination with ciprofibrate (-91%). Ciprofibrate increases PDGF AB content, which is amplified by aspirin pretreatment without correlation with its hypolipidemic action. The increase of PDGF production is suggested to participate in plaque stabilization.

[The effect of monotherapy with ciprofibrate and in combination with acetylsalicylic acid on the spectrum of lipids, thromboxane and fibrinogen in patients with atherosclerosis and hyperlipoproteinemia]. / Vplyv ciprofibrátu v monoterapii a v kombinácii s acetylosalicylovou kyselinou na spektrum lipidov, tromboxán a fibrinogén u pacientov s manifestnou aterosklerózou a hyperlipoproteinémiou.

Ciprofibrate is one of the basic drugs used to lower risk values of lipid parameters and fibrinogen in atherosclerosis patients. Since antiaggregation treatment with acetylsalicylic acid is a complex part of obligatory therapy of these patients, the authors studied the influence of ciprofibrate on chosen lipid parameters, fibrinogen and thromboxane in monotherapy, and also in combination with acetylsalicylic acid (ASA) in patients with advanced atherosclerosis and hyperlipoproteinemia. In the first group of patients (A-C, n = 12) after one month of low-lipid diet acetylsalicylic acid in a dose of 100 mg was administered daily during a period of 2 months followed by addition of 100 mg of ciprofabrate daily during the next 2 months. In the second group of patients (C-A, n = 11) after one month of low-lipid diet the same drugs were administered but in opposite order. Ciprofibrate was most effective in lowering the levels of triacylglycerids (-41%) and VLDL-cholesterol (-34%), but effectively lowered also the values of total cholesterol and LDL-cholesterol. In both studied groups it led to mild increase of HDL-cholesterol levels. Simultaneous administration of ASA did not significantly influence its hypolipemic activity. Ciprofibrate also significantly lowered the level of fibrinogen (-17%). Increase of the total number of platelets by about 10% was not accompanied by changes of the values and production of thromboxane. Simultaneous administration of ASA caused more than 90% inhibition of thromboxane production in monotherapy and in combination with ciprofibrate. Ciprofibrate is an effective hypolipidemic agent, also lowering the level of fibrinogen. Its combination with ASA is adequate, safe and without negative interaction influencing treatment. (Tab. 6, Fig. 1, Ref. 16.)