Confirmation of efficacy of etofibrate against peripheral atherosclerosis in non-human primates which model human lesion types I-VII.
In dyslipidemic or hyperlipidemic patients etofibrate (CAS 31637-97-5, active principle of Lipo-Merz-retard) improves plasma lipoprotein profiles by reducing low density lipoprotein cholesterol and triglycerides. Experimentally, it also promotes fibrinolysis and thrombolysis and reduces the susceptibility of lipoproteins to oxidative stress. In order to investigate the possible efficacy of etofibrate on atherosclerosis, a study in African Green Monkeys was performed. To accelerate atherogenesis, balanced groups of adult male Vervetes (Cercopithecus aethiops) were fed an atherogenic diet, with and without etofibrate, while negative controls received a prudent diet. Total dietary risk exposure was 38 months, with etofibrate treatment during the final 27 months. The etofibrate dose achieved plasma concentrations of clofibric acid comparable to the one achieved clinically. Necropsy demonstrated lesions equivalent to human atherosclerosis types I-VII, which were compared between treatments both macroscopically and microscopically. Peripheral atherosclerosis was significantly less frequent after etofibrate treatment than in positive controls. In aortas, etofibrate probably ameliorated atherogenesis, as defined by proliferation of smooth muscle and foam cells, and accumulation of cholesterol crystals. Effective reduction of plasma cholesterol by etofibrate was confirmed. In conclusion, anti-atherogenic efficacy of etofibrate was demonstrated in a non-human primate model of accelerated atherogenesis. The results on peripheral atherosclerosis confirm the preliminary clinical data in patients suffering from peripheral vascular occlusion.
Fincham
J E
JE
National Research Programme for Nutritional Intervention, Medical Research Council, Tygerberg, South Africa.
Quack
G
G
Wülfroth
P
P
Benadé
A J
AJ
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D001835:Body Weight / Q000502:physiology; D002522:Chlorocebus aethiops; D002995:Clofibric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003331:Coronary Vessels / Q000473:pathology; D004036:Diet, Atherogenic; D004435:Eating / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009929:Organ Size / Q000502:physiology
D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; C009746:etofibrate; D002995:Clofibric Acid