L’athérosclérose, première cause de mortalité dans les pays industrialisés, est une pathologie des grosses et moyennes artères. La réponse inflammatoire secondaire au dépôt des LDL conduit à la formation de la plaque d'athérosclérose. La rupture de la plaque autorise le contact du sang avec le cœur lipidique menant à la formation d'un thrombus. Ce dernier est susceptible de provoquer une occlusion vasculaire dont les conséquences peuvent être fatales.
De nombreux travaux ont montré le rôle primordial joué par les plaquettes dans la survenue d'accidents thrombo-emboliques artériels et, ainsi, les médicaments inhibant les fonctions plaquettaires sont rapidement devenus des molécules de premier choix. Il s’agit des antiactivateurs (l’aspirine, les thiénopyridines et le dipyridamole) et des inhibiteurs de l’agrégation plaquettaire (les antiGPIIb-IIIa), pour lesquels des échecs thérapeutiques ont été cependant recensés.
Sous le terme de résistance aux antiplaquettaires, on regroupe une résistance "clinique" et deux formes de résistance "biologique"
Divers facteurs, qui seront présentés dans ce travail, peuvent être évoqués pour expliquer la résistance aux antiplaquettaires, ils sont d'ordre thérapeutique (la dose administrée, les interactions médicamenteuses…), d'ordre génétique (les mutations ou les polymorphismes sur les cibles moléculaires…) et autres.
La résistance aux antiplaquettaires soulève plusieurs questions: nécessité d’un consensus sur la définition de la résistance et sur le test à utiliser pour la reconnaître; montrer que cette résistance biologique a une signification clinique; définir une attitude thérapeutique adaptative: modification de dose, association
Atherosclerosis, cause of mortality in the industrialized countries, is a pathology of the larges and average arteries. The secondary inflammatory answer to the deposit of the LDL led to the formation of the atherosclerosis plaque. The rupture of this plaque authorizes the contact of blood with the lipid core, leading to the formation of the thrombus. This last is likely to cause a vascular occlusion whose consequences can be fatal.
Many studies showed the major role played by the platelet in occurred the arterial accidents thrombo-embolic and, thus, the drugs inhibiting the platelet functions quickly became of the molecules of first choice. They are the antiactivateurs (aspirin, thiénopyridins and the dipyridamole) and the inhibitors of the plate aggregation (antiGPIIb-IIIa), for which therapeutic failures were however listed.
Under the term of resistance to the antiplatelet, one gathers a "clinical" resistance and two forms of "biological" resistance Various factors, which will be presented in this work, can be evoked to explain resistance to the antiplatelet, they are the therapeutic orders (the administered dose, medicamentous interactions…), the genetic orders (changes or polymorphisms on the molecular targets…) and others.
Resistance to the antiplatelet raises several questions: need for a consensus on the definition of resistance and the test to use to recognize it; to show that this biological resistance has a clinical significance; to define an adaptive therapeutic attitude: modification of amount, association of molecules, change of molecule.
LDL (antiplaquettaires) -antiactivateurs (l’aspirine) (thiénopyridines) (dipyridamole) -antiGPIIb-IIIa)
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