Key result
Simvastatin cuts ADP-induced platelet aggregation ~22% vs. diet alone in primary hypercholesterolemia.
Why the study?
Does simvastatin reduce platelet activation and inflammatory markers in patients with primary hypercholesterolemia?
RCT (n=45)
Randomized
No
Does simvastatin reduce platelet activation and inflammatory markers in patients with primary hypercholesterolemia?
In patients with primary hypercholesterolemia, short-term simvastatin therapy reduces platelet activation, subclinical inflammation, and oxidative stress, effects that correlate strongly with LDL-cholesterol reduction.
Simvastatin may reduce platelet reactivity and inflammation in hypercholesterolemia; hypothesis-generating and requires randomized confirmation before practice change.
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.
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Barale et al. (2018) conducted an RCT in Primary hypercholesterolemia (n=45). Simvastatin vs. Diet alone was evaluated on Platelet aggregation to ADP (maximal aggregation) (22% reduction, p=<0.0001). Simvastatin reduced platelet aggregation to ADP by 22% and improved inflammatory and endothelial markers compared to diet alone in patients with primary hypercholesterolemia.
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