Related Experiment Videos
Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile
G Dangas1, J J Badimon, D A Smith
1Cardiovascular Institute and the Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA.
Insights
Pravastatin significantly reduced LDL cholesterol, improved the fibrinolytic profile, and decreased thrombus formation in patients with and without coronary artery disease. These findings may explain pravastatin
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- Lowering cholesterol reduces cardiovascular events, but effects on hemostasis and thrombosis are not fully understood.
- Lipid-lowering therapy's impact on the complete thrombotic profile requires investigation.
Purpose of the Study:
- To assess pravastatin's effects on systemic fibrinolysis and thrombus formation.
- To determine if lipid lowering influences the entire hemostatic and thrombotic profile.
Main Methods:
- 93 patients with high LDL cholesterol were studied prospectively.
- Coronary artery disease (CAD) patients received pravastatin; non-CAD patients received pravastatin or placebo.
- Thrombus formation was measured ex vivo using a perfusion chamber system over six months.
Main Results:
- Pravastatin decreased LDL cholesterol by 30% and reduced plasminogen activator inhibitor-1 and tissue plasminogen activator antigen.
- Thrombus formation decreased significantly in pravastatin-treated groups, correlating with LDL reduction.
- No significant changes were noted in several other hemostatic markers; fibrinogen increased slightly.
Conclusions:
- Pravastatin therapy improves fibrinolysis and reduces thrombus formation in patients with and without CAD.
- These effects may contribute to pravastatin's benefits in cardiovascular disease prevention.
Objectives:
The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions.
Background:
Lowering cholesterol (C) decreases clinical events in coronary artery disease (CAD) patients, but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted.
Methods:
We prospectively studied 93 stable patients with untreated low-density lipoprotein cholesterol (LDL-C) >145 mg/dl. The CAD patients received pravastatin, and non-CAD patients were randomized to pravastatin versus placebo (double-blind). Thrombus formation upon an injured vascular surface was assessed in a substudy of 40 patients with a previously validated ex vivo perfusion chamber system. Systemic hemostatic markers and thrombus formation were evaluated at baseline, three and six months.
Results:
Placebo produced no changes in either the lipid profile, any of the hemostatic markers, or the ex vivo thrombus formation. Both pravastatin groups (CAD and non-CAD) showed decreased LDL-C by 30% within 6 weeks (188 to 126 mg/dl, p < 0.001 vs. baseline), and decreased plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline (15% to 18% decrease at 3 months and 21% to 23% at 6 months). For the tissue plasminogen activator antigen, CAD and non-CAD groups showed significant decreases at 6 months compared to baseline (10% and 13%, respectively). No significant changes were observed with treatment in d-dimer, fibrinopeptide A, prothrombin fragment F1.2, factor VIIa, von Willebrand factor, or C-reactive protein. Fibrinogen levels were significantly increased at 6 months compared to baseline, though still below the upper normal limit. In the perfusion chamber substudy, there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline (by 21% and 34%, respectively). The CAD patients showed decreases in thrombus formation by 13% at 3 months, and by 16% at 6 months. The change in LDL-C- correlated modestly with the change in thrombus formation (r = 0.49; p < 0.01).
Conclusions:
Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD. These early effects may, in part, explain the benefit rendered in primary and secondary prevention of CAD.