The effects of hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors on platelet thrombus formation.
BACKGROUND
Hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors (HMG CoA RIs) markedly improve the lipid profile of patients with hypercholesterolemia, but the magnitude and time course of the effect of these drugs on other risk factors for atherosclerosis are not well defined.


METHODS
We employed a random assignment, double-blind design to compare the effect of 8 weeks of HMG CoA RI therapy with either pravastatin (40 mg QD; n=12) or simvastatin (20 mg QD; n=12) with placebo (n=13) on serum lipids, platelet thrombus formation (PTF), and markers of inflammation and thrombosis in patients with coronary artery disease. PTF was measured using a validated ex vivo perfusion chamber system.


RESULTS
Total and LDL cholesterol decreased 20.3 +/- 12.7% and 31.4 +/- 16.5% in the HMG CoA RI group and were unchanged with placebo (P<0.01). Triglycerides also decreased 15.3 +/- 22.5% with HMG CoA RI therapy, but increased 8.4 +/- 30.0% with placebo (P=0.01). PTF increased 54.1 +/- 89.0% with placebo and decreased 8.0 +/- 46.82% with HMG CoA RI treatment (P<0.01).


CONCLUSIONS
HMG CoA RI therapy with pravastatin or simvastatin reduces PTF after only 8 weeks of therapy. Such lipid effects may contribute to the prompt reduction in cardiovascular events noted in some clinical trials.
Thompson
Paul D
PD
Section of Preventive Cardiology, Division of Cardiology, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA. pthomps@harthosp.org
Moyna
Niall M
NM
White
C Michael
CM
Weber
Kelly M
KM
Giri
Satyendra
S
Waters
David D
DD
D000368:Aged; D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000517:prevention & control; D003328:Coronary Thrombosis / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage*; D011336:Probability; D012016:Reference Values; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D017035:Pravastatin