High post‐treatment platelet reactivity identified low‐responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome

Abstract

Summary. Background and objectives: Low response to antiplatelet therapy may be a risk factor for the development of ischemic complications in patients with non-ST segment elevation acute coronary syndrome (NSTE ACS) undergoing coronary stenting. Methods: We prospectively studied the platelet response to both clopidogrel and aspirin in 106 NSTE ACS consecutive patients undergoing percutaneous coronary intervention (PCI) with stenting. A single post-treatment blood sample was obtained just before PCI and analyzed by platelet aggregometry using both ADP and arachidonic acid (AA) as agonists to explore the responses to clopidogrel and aspirin, respectively. Patients were divided into quartiles according to the ADP or AA induced maximal intensity of platelet aggregation. Patients of the highest quartile (quartile 4) were defined as the Ôlow-respondersÕ. Results: Twelve recurrent cardiovascular (CV) events occurred during the 1-month follow-up. Clinical outcome was significantly associated with platelet response to clopidogrel [Quartile 4 vs. 1, 2, 3: OR (95% CI) 22.4 (4.6-109)]. Low platelet response to aspirin was significantly correlated with clopidogrel low response (P ¼ 0.003) but contributed less to CV events [OR (95%CI): 5.76 (1.54-35.61)]. Conclusions: A post-treatment ADP-induced platelet aggregation performed just before PCI identifies low responders to dual antiplatelet therapy with an increased risk of recurrent CV events.

Characterization and Evaluation of Clopidogrel Response Testing in a Community Hospital Setting

“…Unfortunately, there was a trend towards increased 90 day rehospitalization rates due to recurrent thrombosis or bleeding in both the patients where no changes to therapy were made and patients where clopidogrel was discontinued without any thing to take its place. These results are similar to prior studies demonstrating that patients with low platelet inhibition are more likely to experience rethrombosis and ischemia than patients with higher levels of platelet inhibition [2][3][4][6][7][8][9][10][11].…”

“…Overall stent thrombosis was 3.1%; however this rate was 8.6% in nonresponders to clopidogrel compared to 2.3% in patients responding to clopidogrel (p<0.001) [7]. Similar results have been published in several other trials demonstrating the correlation between higher atherothrombotic events and lower platelet inhibition [8][9][10][11]. There are also studies using the VerifyNow P2Y 12 Test which demonstrate the correlation between higher atherothrombotic events and lower platelet inhibition [12][13][14][15][16].…”

Evidence that pre‐existent variability in platelet response to ADP accounts for ‘clopidogrel resistance’

“…Thus, some [5,8,9], but not other [25], very small studies suggest that patients with higher residual platelet reactivity after the initiation of clopidogrel therapy have more subsequent major adverse clinical outcomes. Higher doses of clopidogrel [26][27][28][29], or other antiplatelet therapy, may therefore be beneficial, especially in those patients with greater platelet reactivity to ADP, measured either before or after clopidogrel therapy.…”

High-residual platelet activity despite dual antiplatelet treatment associated with subacute stent thrombosis

“…Response variability and resistance to clopidogrel therapy was first reported in 2003 [17]. Since then, many studies and registries suggested a relationship between high post-treatment platelet reactivity and clopidogrel nonresponsiveness in patients undergoing PCI, especially increased ischemic events including stent thrombosis [7,8,18,19]. All these data are from retrospective and prospective studies.…”