Mechanisms for Antiplatelet Action of Statins

Abstract

Hydroxymethyl-glutaryl coenzyme A reductase inhibitors (statins) offer important benefits for the large populations of individuals at high risk for coronary heart and cerebrovascular disease. the overall clinical benefits observed with statin therapy appear to be greater than what might be expected from changes in lipid profile alone, suggesting that the beneficial effects of such drugs may extend beyond their effects on serum cholesterol. Platelet hyperactivity is a key step in atherothrombosis and experimental data suggest that statins could exert an antiplatelet effect which could be involved in their protective action. In the present review we report of the major studies in humans showing the effect of statins on platelets, especially by the more sensitive methods to explore platelet function such as cytofluorymetric detection of specific proteins. Moreover we describe the putative mechanisms involved in platelet deactivation with particular regard to the effects related to cholesterol reduction or beyond lipid-lowering. Indeed, data from several studies suggest some differences among compounds in terms of timing of action by modulation of several activating pathways which could take part either in the early, cholesterol-lowering independent, effects in the acute phase of vascular disease or during chronic treatment.

Effect of statins on platelet function in patients with hyperlipidemia

“…The list of effects of statins, other than hypolipemic, is still expanding and includes: a decrease in expression or activity of inflammatory agents and metalloproteinases, and an influence on endothelial function and the hemostatic system [22]. Results of studies on the effects of statin therapy on platelet function depend on the dose of statin, method of evaluation of platelet activity, and the use of agonists and other agents (e.g.…”

Treatment With Ezetimibe Plus Low-Dose Atorvastatin Compared With Higher-Dose Atorvastatin Alone

“…Platelet inhibition and anti-inflammatory effects. Inhibition of platelets by statin therapy is a well-documented dose-dependent effect (3)(4)(5)(6)(7)(8)(9)(10). Cholesterol-dependent and -independent mechanisms may contribute to it.…”

“…The reduced mortality is attributed not only to the lowering of LDL-C but also to the numerous pleiotropic effects of statins (3)(4)(5)(6). The inhibition of platelets by statins is well documented in patients with hypercholesterolemia and CAD as well as in healthy individuals (7)(8)(9)(10).…”

Collagen Receptors as Potential Targets for Novel Anti-Platelet Agents

“…There is some controversy about whether this is really hard evidence for a role of rafts or not. On the other hand there is speculation that one of the effects of statins in reducing cardiovascular disease may be by reducing cholesterol in platelet membranes [95] and hence signaling through receptors such as GPVI and GPIb. Investigation of the effects of various statins on platelet function might enable their targeted use in reducing platelet activity perhaps in conjunction with other antiplatelet agents like clopidogrel.…”