title: Evidence of combined therapy of dyslipoproteinemia by HMG-CoA reductase inhibitors and "essential" phospholipids.
abstract: Platelets are involved in the initiation of atheromas and arterial thrombosis and thus may play a cardinal role in the pathogenesis of myocardial and cerebral infarction. In 18 patients with coronary artery disease and hypercholesterolemia resistant to low-lipid diet a 12 week treatment with lovastatin (HMG-CoA reductase inhibitor) leads to the reduction of total cholesterol, LDL-cholesterol and triglycerides but also to a marked increase of platelet activity. Lovastatin is an inactive lacton prodrug which must be enzymatically or chemically transformed to the active form. In in-vitro experiments, it was discovered that both chemically hydrolysed lovastatin and plasma containing lovastatin metabolites stimulate induced platelet aggregation in whole blood samples. "Essential" phospholipids (Lipostabil) added to the blood samples in concentrations according to those which are used clinically prevent this stimulation. This corresponds to data obtained earlier from Lipostabil-treated ischemic heart disease patients. Besides a lipid-lowering effect Lipostabil showed a 50% reduction of spontaneous aggregates in plasma, an increase of the susceptibility threshold to aggregation inducers and a decrease of the platelet aggregation amplitude in whole blood samples. Therefore, it would be promising to combine the therapy by lovastatin with "essential" phospholipids possessing a remarkable improving effect on the platelet function based on a molecular action independent of their moderate lipid-reducing action.
authors.affiliation: Cardiology Institute, S. Petersburg, Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Gurevich
authors.forename: B B
authors.initials: BB
authors.lastname: Bondarenko
authors.forename: I A
authors.initials: IA
authors.lastname: Mikhailova
authors.forename: N I
authors.initials: NI
authors.lastname: Kasennova
authors.lastname: Popov YuG
authors.lastname: Astashkina
authors.forename: T D
authors.initials: TD
authors.lastname: Le Van Thach
mesh_terms: D000328:Adult; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; C005152:lipostabil; D002784:Cholesterol; D008148:Lovastatin