Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction

Abstract

Background-Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur. Methods and Results-The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segmentelevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103Ϯ8% of baseline), ADP-induced aggregation was reduced to 69Ϯ3%, 58Ϯ7%, and 33Ϯ12% of baseline, respectively, in patients in quartiles 2 through 4 (PϽ0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow conditions, assessed by the cone-and-plate(let) analyzer method, were reduced significantly less in the first quartile than in quartiles 2 through 4. Whereas 40% of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up, only 1 patient (6.7%) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event (Pϭ0.007). Conclusions-Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.

Platelet-Mediated Thrombosis

“…44 At the same time, Matetzky et al, using aggregometry, observed that patients undergoing primary PCI for ST-segment-elevation MI who were in the lowest quartile of clopidogrel responsiveness had the highest rates of ischemic events during follow-up. 45 Subsequently, it was suggested that the level of on-treatment platelet reactivity is a better risk predictor compared with clopidogrel responsiveness. 46 Small early studies suggested that ischemic event occurrence was not linearly related to on-treatment platelet reactivity but rather occurred above a moderate level of platelet reactivity to ADP.…”

“…44 Similarly, ADP-induced P2Y 12 receptor assessed by various techniques was correlated with stent thrombosis and longterm post-PCI ischemic event occurrences and bleeding (Table 1). 32,44,45,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] Some studies used receiver operating characteristic curve analysis to define an optimal cutoff of on-treatment platelet reactivity for predicting thrombotic risk. In 2010, a consensus statement proposed cutoff values based on receiver operating characteristic curve analysis for different platelet function assays to be used in future studies of personalized antiplatelet therapy.…”

Impact of Intravenous Lysine Acetylsalicylate Versus Oral Aspirin on Prasugrel-Inhibited Platelets

“…5,6 Clopidogrel, the most worldwide used P2Y 12 -ADP receptor antagonist, presents some limitations, such as high interand intraindividual variability or slow onset of action, despite loading dose (LD), which has been related with an increase of cardiovascular events. [7][8][9] This finding has been overcome with new ADP-antagonists, like prasugrel or ticagrelor. …”

Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

“…However, since 2003, studies suggested that the pharmacodynamic effect of clopidogrel considerably varies among individuals, implying that it may lead to the occurrence of ischemic or bleeding events [3,4]. These events were once known as clopidogrel resistance, or clopidogrel non-responsiveness, and they are now identified as high on-treatment platelet reactivity (HTPR).…”