title: No influence of simvastatin treatment on platelet function in vivo in patients with hypercholesterolemia.
abstract: Hypercholesterolemia is associated with platelet activation. Reduction of plasma cholesterol levels by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin has been found to improve certain aspects of platelet function in vitro and in vivo, but controlled trials are largely lacking. The present randomized, double-blind, crossover study was performed to evaluate whether 10- to 12-week treatment with simvastatin or placebo affects platelet function in vivo in 23 hypercholesterolemic men. Measurements were performed at rest and during mental stress. Simvastatin treatment reduced plasma total cholesterol levels by 18 +/- 2% and low density lipoprotein cholesterol levels by 26 +/- 2% (P < .001 for both), whereas high density lipoprotein cholesterol levels increased slightly (6 +/- 2%, P < .05). Platelet aggregability as assessed by filtragometry ex vivo was unaffected by simvastatin treatment both at rest and during mental stress. Plasma beta-thromboglobulin levels, which reflect platelet secretion, were also unaltered by simvastatin treatment both at rest (antilog of the mean: 20.2 versus 20.0 ng/mL during placebo) and during mental stress. Moreover, nocturnal excretion of 11-dehydrothromboxane B2 in urine did not differ between placebo and active treatment: 218 versus 216 ng/mmol creatinine, respectively. The corresponding values for urinary excretion of high-molecular-weight beta-thromboglobulin were 1.78 versus 1.92 ng/mmol creatinine. Thus, simvastatin treatment had no clear-cut effect on platelet function, as assessed by four different in vivo related platelet function variables, in hypercholesterolemic men.
authors.affiliation: Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden. broij@mb.ks.se
authors.forename: A
authors.initials: A
authors.lastname: Bröijersén
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
authors.forename: B
authors.initials: B
authors.lastname: Leijd
authors.forename: B
authors.initials: B
authors.lastname: Angelin
authors.forename: P
authors.initials: P
authors.lastname: Hjemdahl
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy* / Q000652:urine; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D012146:Rest; D019821:Simvastatin; D013315:Stress, Psychological; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013954:Thyroglobulin / Q000032:analysis / Q000652:urine
chemical_list: D004791:Enzyme Inhibitors; D008055:Lipids; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D013954:Thyroglobulin; D008148:Lovastatin; D019821:Simvastatin