Simvastatin 40 mg for 2 months significantly reduced platelet aggregation to ADP (p=0.0001) and collagen (p=0.0001), and decreased inflammatory markers like IL-6 (p=0.0034).
RCT (n=45)
Does simvastatin 40 mg added to diet reduce platelet activation, inflammation, and endothelial dysfunction in hypercholesterolemic patients?
Simvastatin 40 mg daily reduces platelet activation, subclinical inflammation, and endothelial dysfunction in patients with primary hypercholesterolemia, with LDL-C levels being the strongest predictor of platelet reactivity.
p-value: p=0.0001
Background . Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation. Methods. In hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1 β , -5, -6, -7, -8, -9, -10, -12, and -13, IFN- γ , IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2’-deoxyguanosine). Results . After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p<0.0001), IFN- γ (p<0.0001), VEGF (p<0.0001), sE-selectin (p<0.0001), sCD-40L (p<0.0001), sP-selectin (p=0.003), and 8-OH-2’-deoxyguanosine (p<0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN- γ , E-selectin, sCD-40L, 8-OH-2’-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity. Conclusion . In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis.
Barale et al. (Mon,) conducted a rct in Hypercholesterolemia (n=45). Simvastatin vs. Diet alone was evaluated on Platelet aggregating responses to ADP, collagen, and arachidonic acid, and markers of inflammation and endothelial activation (p=0.0001). Simvastatin 40 mg for 2 months significantly reduced platelet aggregation to ADP (p=0.0001) and collagen (p=0.0001), and decreased inflammatory markers like IL-6 (p=0.0034).