title: A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity for Outcome Validation Effort) study.
abstract: OBJECTIVE
  This study sought to validate the ability of the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) in predicting both ischemic and bleeding events after elective percutaneous coronary intervention (PCI).
  
  
  BACKGROUND
  High and low levels of platelet reactivity are associated with ischemic and bleeding events, respectively, after PCI.
  
  
  METHODS
  A total of 732 patients on dual antiplatelet therapy undergoing elective PCI were recruited. Platelet reactivity was measured before PCI. The primary endpoint was the 30-day incidence of net adverse clinical events (NACE), defined as the occurrence of ischemic or bleeding events, in relation to P2Y(12) reaction unit (PRU) distribution.
  
  
  RESULTS
  At receiver-operating characteristic curve analysis, PRU values could significantly discriminate between patients with and without bleeding events (area under the curve [AUC]: 0.72; 95% confidence interval [CI]: 0.65 to 0.80; p < 0.0001) and those with and without ischemic events (AUC: 0.68; 95% CI: 0.61 to 0.76; p < 0.0001). The optimal cutoffs for bleeding (PRU ≤ 178) and ischemic events (PRU ≥ 239) were used to define 3 groups: low platelet reactivity (LPR) (LPR = PRU ≤ 178), normal platelet reactivity (NPR) (NPR = PRU 179 to 238), and high platelet reactivity (HPR) (HPR = PRU ≥ 239). The incidence of NACE was 14.1% in the LPR group, 7.8% in the NPR group (p = 0.025 vs. LPR group), and 15.4% in the HPR group (p = 0.005 vs. NPR group). At multivariate analysis, PRU values in the NPR group were an independent predictor of reduced risk of 30-day NACE (odds ratio: 0.47, 95% CI: 0.27 to 0.81).
  
  
  CONCLUSIONS
  A therapeutic window for platelet reactivity measured with the VerifyNow P2Y12 assay can be identified using specific thresholds that define a group of patients at lower risk for both ischemic and bleeding events. Adjunctive measures may be beneficial in patients with higher or lower platelet reactivity in order to improve clinical outcomes after PCI.
authors.affiliation: Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy. f.mangiacapra@unicampus.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Mangiacapra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Patti
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barbato
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Peace
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ricottini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vizzi
authors.forename: Laura
authors.initials: L
authors.lastname: Gatto
authors.forename: Andrea
authors.initials: A
authors.lastname: D'Ambrosio
authors.forename: Bernard
authors.initials: B
authors.lastname: De Bruyne
authors.forename: William
authors.initials: W
authors.lastname: Wijns
authors.forename: Germano
authors.initials: G
authors.lastname: Di Sciascio
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D001530:Belgium; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy*; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000209:etiology; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology; D016017:Odds Ratio; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012372:ROC Curve; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12