Summary
In addition to lowering cholesterol, statins may reduce platelet activity and exert
beneficial non-lipid (pleiotropic) effects. We evaluated the effects of two different
simvastatin based treatment regimens on platelet reactivity in patients with dysglycemia
and coronary artery disease (CAD). Thirty-two patients with type 2 diabetes or impaired
glucose tolerance and stable CAD received six weeks of double-blind treatment with
simvastatin 80 mg daily (S80; n=16) or ezetimibe 10 mg and simvastatin 10 mg daily
(E10/S10; n=16). Total and low-density lipoprotein (LDL) cholesterol, and high sensitivity
C-reactive protein (CRP) decreased similarly in the two groups. LDL (mM) decreased
from 3.2 ± 0.6 to 1.7 ± 0.7 with E10/S10 and from 3.0 ± 1.0 to 1.4 ± 0.5 with S80
treatment. Platelet function was evaluated by whole blood flow cytometry and turbidimetric
aggregometry with agonist stimulation ex vivo before and after treatment. Neither treatment affected basal or adenosine diphosphate
(ADP)- or thrombin-induced platelet P-selectin expression, or fibrinogen binding,
or platelet-leukocyte aggregation. Similarly, neither treatment affected ADP-induced
platelet aggregation. In conclusion, lipid lowering treatment with high dose simvastatin
or low dose simvastatin plus ezetimibe did not exert any substantial inhibitory effects
on the basal or agonist-stimulated activity of circulating platelets in patients with
stable CAD and type 2 diabetes or impaired glucose tolerance.
Keywords
Simvastatin - ezetimibe - ADP - thrombin - platelet activation