The actions of lovastatin on platelet function and platelet eicosanoid receptors in type II hypercholesterolaemia. A double-blind, placebo-controlled, prospective study.
We have studied the effects of 12 weeks of lovastatin (20 mg per day) on platelet function and thromboxane formation in 18 patients with type II hypercholesterolaemia in a double-blind, placebo-controlled, prospective study. Lovastatin significantly reduced total serum and LDL-cholesterol by 20% and 25% respectively. Washed platelets of lovastatin-treated patients had significantly reduced collagen-induced aggregation and thromboxane formation ex vivo. There was no change in ADP-induced platelet aggregation, but a significant increase in prostacyclin (iloprost)-stimulated platelet cyclic AMP concentrations in lovastatin-treated patients. This was associated with a significant increase in the number of prostacyclin receptors in platelet membranes prepared from lovastatin-treated patients. There was also an increase in platelet thromboxane receptors. There were no such changes in the placebo group. These data confirm our original observation of normalization of platelet function in hypercholesterolaemia by HMGCoA reductase inhibitors and suggest changes in platelet membrane composition at the megakaryocyte level as a possible site of action.
Kaczmarek
D
D
Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Hohlfeld
T
T
Wambach
G
G
Schrör
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011446:Prospective Studies; D018055:Receptors, Eicosanoid / Q000187:drug effects*; D015290:Second Messenger Systems / Q000187:drug effects; D013931:Thromboxanes / Q000378:metabolism
D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D018055:Receptors, Eicosanoid; D013931:Thromboxanes; D008148:Lovastatin; D000242:Cyclic AMP