title: Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: a potential antiplatelet therapeutic target.
abstract: Platelets play a central role in the genesis of post-percutaneous coronary intervention (PCI) ischemic events. High post-procedural platelet reactivity to adenosine diphosphate (HPR(ADP)) 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 microM ADP-induced platelet aggregation (46 +/- 14% vs. 30 +/- 17%, p < 0.001) and 20 microM 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 microM ADP stimulation and >59% aggregation following 20 microM ADP stimulation (HPR(ADP)) were associated with 58 and 54% of ischemic events, respectively. Multivariate Cox regression demonstrated a significant relation between event occurrence and post-procedural HPR(ADP) cutpoints (5 microM ADP, OR=3.9, and 20 microM 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.
authors.affiliation: Sinai Center for Thrombosis Research, Department of Medicine, Sinai Hospital, Baltimore, Maryland 21215, USA. pgurbel@lifebridgehealth.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Antonino
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bliden
authors.forename: Joseph
authors.initials: J
authors.lastname: Dichiara
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Suarez
authors.forename: Anand
authors.initials: A
authors.lastname: Singla
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D000244:Adenosine Diphosphate