Pravastatin and simvastatin improves acetylsalicylic acid-mediated in vitro blood platelet inhibition

Background: Insight into the pathophysiology of atherothrombosis indicates that an integrated risk factor approach, focusing particularly on the management of dyslipidaemia (with statins) and thrombosis (with ASA), may constitute an optimal therapeutic approach. We investigated whether pravastatin, simvastatin and atorvastatin may directly modulate under in vitro conditions the reactivity of blood platelets originating from healthy volunteers. In addition, we analysed the influence of statins on the platelet sensitivity to ASA under such conditions.

Materials and methods: We monitored collagen- or ADP-induced platelet aggregation, CD36, PAC-1 and CD62 expression on platelet surface and thromboxane generation after incubation with pravastatin, simvastatin, atorvastatin and/or ASA.

Results: The incubation of whole blood with simvastatin and pravastatin significantly decreased CD36 expression. In the presence of 50 μM ASA, simvastatin and pravastatin significantly reduced the PAC-1 expression (30% reduction for simvastatin, P < 0·01, and 15% reduction for pravastatin, P < 0·01), platelet aggregation (20% reduction for both statins, P < 0·01) and thromboxane generation (35% reduction for simvastatin, P < 0·001, and 30% reduction for pravastatin, P < 0·001) compared to ASA alone. Atorvastatin changed neither baseline platelet aggregation nor ASA-mediated platelet inhibition.

Conclusions: Our results suggested that statins may directly interact with platelet membranes or may modulate a signalling pathway in platelets (the pleiotropic effects of statins). It is possible that the statin effect on CD36 and ASA-mediated protein acetylation can be reached by the modulation of a distribution or a function of membrane-associated proteins. Further studies are certainly needed to better elucidate the mechanism(s) underlying the statins' effects on platelet sensitivity to ASA.