Clopidogrel Resistance

Abstract

Clopidogrel resistance has been used as one of the terms employed in the literature to describe different degrees of ex vivo low platelet inhibition after clopidogrel administration. In addition to the diverse nomenclature, the characterisation of clopidogrel resistance has also been problematic because different authors have given different definitions. The mechanisms responsible for this decreased platelet response are not yet clearly defined, some hypotheses have been put forward but not yet demonstrated. Although there have been no large prospective studies demonstrating that the degree of platelet inhibition is directly related to clinical outcomes, several recent studies and reports have shown an association between less platelet inhibition and more adverse events after percutaneous coronary interventions with clopidogrel therapy suggesting that clopidogrel resistance may be a marker for increased risk of recurrent cardiovascular events. Larger scale investigations are needed to support these findings.

Effect of ASA dose doubling versus switching to clopidogrel on plasma inflammatory markers concentration in patients with type 2 diabetes and high platelet reactivity: The AVOCADO study

“…Several previous studies demonstrated anti--inflammatory effect of low doses of ASA and clopidogrel, mainly in patients with CAD [18][19][20][21][22][23][24][25]. The results of subanalysis of Physician's Health Study suggested that cardioprotective effect of ASA correlated with its anti-inflammatory effect [26].…”

P2Y12Platelet Receptors: Importance in Percutaneous Coronary Intervention

“…Doses higher than 600 mg did not lead to more antiaggregation, since these doses did not lead to an increase in the concentration of the active metabolite 4 .…”

“…Thus, though not capable of sustaining platelet aggregation, they contribute to collagen-induced activation 4 .…”

“…The endothelial monolayer acts as an antithrombotic surface, since it does not allow the interaction of platelets and sub endothelial proteins and produces prostacyclin I2 and nitric oxide, which are, both, platelet activation inhibitors. Endothelial cells also express the CD39 enzyme, which converts adenosine triphosphate (ATP) to ADP and ADP to adenosine monophosphate (AMP), avoiding platelet activation by ATP and ADP 4 .…”

“…In response to ADP-mediated activation, calcium is mobilized from platelet storage, leading to conformational change and transient aggregation. This receptor has a key role in the beginning of ADP-induced activation, but, for the effective stabilization of platelet thrombus, the activation of other receptors is required 4,5 .…”