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No influence of simvastatin treatment on platelet function in vivo in patients with hypercholesterolemia
A Bröijersén1, M Eriksson, B Leijd
1Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden. broij@mb.ks.se
Insights
Simvastatin effectively lowers cholesterol in hypercholesterolemic men but does not significantly impact platelet function, as measured by several in vivo markers, during rest or stress.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- Hypercholesterolemia is linked to increased platelet activation.
- Simvastatin, a statin, may influence platelet function, but robust clinical evidence is limited.
Purpose of the Study:
- To investigate the effect of simvastatin on in vivo platelet function in hypercholesterolemic men.
- To assess platelet response to simvastatin during rest and mental stress.
Main Methods:
- A randomized, double-blind, crossover study involving 23 hypercholesterolemic men.
- Evaluated platelet aggregability, beta-thromboglobulin levels, and urinary 11-dehydrothromboxane B2 and high-molecular-weight beta-thromboglobulin excretion.
- Measurements taken at rest and during mental stress.
Main Results:
- Simvastatin significantly reduced total cholesterol (18%) and LDL cholesterol (26%), with a slight increase in HDL cholesterol.
- Platelet aggregability, beta-thromboglobulin levels, and urinary thromboxane metabolites remained unchanged.
- No significant effect on platelet function markers was observed during rest or mental stress.
Conclusions:
- Simvastatin treatment effectively lowers cholesterol in hypercholesterolemic men.
- Despite cholesterol reduction, simvastatin did not demonstrate a clear impact on assessed in vivo platelet function markers.
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.