Statins inhibit platelet activation. Washed human platelets were treated for 5 minutes with increasing concentration of simvastatin or fluvastatin, prior to stimulation for 90 seconds with collagen-related peptide CRP-XL (0.5 μg mL⁻¹) and aggregation measured at 37°C under constant stirring conditions. Numerical data represent the percentage aggregation compared with control, mean ± SEM (n = 4) (A-B). The effect of simvastatin or fluvastatin on fibrinogen binding and P-selectin exposure prior to stimulation with CRP-XL (1 μg mL⁻¹) was measured in human whole blood by flow cytometry. Numerical data represent the percentage of fibrinogen binding and P-selectin exposure compared with control, mean ± SEM (n = 4) (C-D). Washed human platelets were treated for 5 minutes with increasing concentrations of simvastatin or fluvastatin, prior to stimulation for 90 seconds with collagen-related peptide CRP-XL (0.5 μg mL⁻¹). Changes in ATP concentration were used as a measure of dense-granule secretion and monitored simultaneously with aggregation in an optical lumi-aggregometer using a luciferase detection system. Numerical data represent the percentage of ATP release compared with control, mean ± SEM (n = 4) (E-F). Platelets stimulated with CRP-XL (1 μg mL⁻¹) in the presence or absence of simvastatin were analyzed by immunoblotting with anti-phosphotyrosine antibody (4G10) and anti-phospho-site antibodies for Syk (Y323), PLC (Y1197), Fyn (Y59), and Lyn (Y396) (G-I). Blots are representative of 4 different experiments (n = 4), t test, P > .05 (nonsignificant [NS]), *P < .05, **P < .01.