Aspirin and clopidogrel hyporesponsiveness and nonresponsiveness in patients with coronary artery stenting

Abstract

Patients undergoing coronary artery stenting receive an antiplatelet regimen to reduce the risk of antithrombotic complications. Current guidelines recommend the use of acetyl salicylic acid (aspirin) and clopidogrel as evidenced by large clinical trials. There has been a concern about variable responses of patients to aspirin and clopidogrel which may predispose them to subacute stent thrombosis or late stent thrombosis. Up to 25% of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) were found to have hyporesponsiveness or resistance to clopidogrel which may predispose them to recurrent events. Dual antiplatelet regimen is a standard therapy in these patients and there is always a concern about variable responses to aspirin and clopidogrel predisposing them to acute coronary syndrome (ACS). Prevalence of this hyporesponsiveness or resistance may be due to noncompliance, genetic mutations, co-morbid situations and concomitant use of other drugs. This issue is of considerable importance in the era of coronary drug eluting stents when a long-term dual antiplatelet regimen is needed. This paper is a review for clinicians taking care of such patients with hyporesponsiveness or nonresponsiveness to dual antiplatelet regimen.

Red cell distribution width, other hematological parameters and atherogenic index of plasma in patients with clopidogrel and aspirin resistance

“…MPV, PDW, or PCT values were not different between groups, similar to Nada [21]'s study, which observed that diabetic patients receiving aspirin or clopidogrel did not show significant differences in MPV when compared with controls [19]. Hyperglycaemia may decrease the effectiveness of antiplatelet therapy by increasing reactive oxidant species and lead to aspirin resistance by binding to thromboxane receptors, whereas hypercholesterolaemia may blunt aspirin's effect on thrombin [23,24]. Genetics also play a role in patient response to aspirin as polymorphisms of platelets membranes postulated to cause aspirin resistance.…”

Clinical importance of aspirin and clopidogrel resistance

“…Therefore, it is imperative to understand this variable response or hyporesponsiveness to aspirin and clopidogrel in some patients. A clear definition of this response should be established and, based on this, one may then be able to categorize patients as a responders, hyporesponders, nonresponders, or resistant and thus manage their therapeutic regimen accordingly [9][10][11][12] .…”

“…COX-1 is rapidly resynthesized by nucleated cells, such as endothelial cells, and therefore the effect of aspirin on nucleated cells lasts only for a relatively short time [4][5][6][7][8] . In contrast, the effect of aspirin on platelets (anucleate cells) lasts for the life of the platelets (7-10 d) [9] ( Figure 1). …”

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

“…There is no consensus on the characterization of aspirin and clopidogrel resistance, and its prevalence remains unclear [10,11]. This resistance is generally accepted to be characterized by incomplete suppression of platelet aggregation, as assessed by platelet-function tests.…”