Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: A potential antiplatelet therapeutic target

Platelets play a central role in the genesis of post-percutaneous coronary intervention (PCI) ischemic events. High post-procedural platelet reactivity to adenosine diphosphate (HPRADP) may be a risk factor for ischemic events after PCI. The study was designed to evaluate a cutpoint of platelet reactivity that is associated with the occurrence of ischemic events after PCI. Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 297 consecutive patients undergoing non-emergent PCI. Patients were prospectively followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Eighty-one patients (27%) suffered ischemic events. Patients with ischemic events had higher 5 µM ADP-induced platelet aggregation (46 ± 14% vs. 30 ± 17%, p < 0.001) and 20 µM ADP-induced platelet aggregation (60 ± 13% vs. 43 ± 19%, p < 0.001) compared to patients without ischemic events. Using a combined receiver operator curve analysis, cutpoints of >46% aggregation following 5 µM ADP stimulation and >59% aggregation following 20 µM ADP stimulation (HPRADP) were associated with 58 and 54% of ischemic events, respectively. Multivariate Cox regression demonstrated a significant relation between event occurrence and post-procedural HPRADP cutpoints (5 µM ADP, OR=3.9, and 20 µM ADP, OR=3.8, p < 0.001 for both). High post-procedural platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data support a potential therapeutic target for antiplatelet therapy based on the results of an ex vivo platelet function test. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.