title: Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).
abstract: OBJECTIVE
  This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines.
  
  
  BACKGROUND
  New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes. However, bleeding complications remain the Achilles' heel of antiplatelet therapy, and platelet monitoring could be useful to evaluate this risk.
  
  
  METHODS
  A total of 1,542 consecutive patients undergoing coronary stenting for ACS were included in the present study (287 taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel 10 mg).
  
  
  RESULTS
  During 6-month follow-up, 9% of patients (n = 139) experienced nonaccess site-related Bleeding Academic Research Consortium bleeding complications. These patients were more often women and nondiabetic and had lower PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP ≤10% to predict bleeding events with a sensitivity of 17% and a specificity of 97%. Although prasugrel was the main predictor of VLTPR in the whole population (odds ratio: 10.2, 95% confidence interval: 3.0 to -34.2; p < 0.001), VLTPR was the strongest and independent predictor of bleeding (odds ratio: 4.7, 95% confidence interval: 2.7 to 8.3; p < 0.001).
  
  
  CONCLUSIONS
  The present study identified VLTPR (PRI VASP ≤10%) as the strongest predictor of bleeding complications in patients treated with thienopyridines. This marker could be useful for tailored therapy and bleeding prevention.
authors: Département de Cardiologie, CHU Timone, Marseille, France. thomas.cuisset@ap-hm.fr
authors: Thomas
authors: T
authors: Cuisset
authors: Charlotte
authors: C
authors: Grosdidier
authors: Anderson Diendonné
authors: AD
authors: Loundou
authors: Jacques
authors: J
authors: Quilici
authors: Marie
authors: M
authors: Loosveld
authors: Laurence
authors: L
authors: Camoin
authors: Mathieu
authors: M
authors: Pankert
authors: Shirley
authors: S
authors: Beguin
authors: Marc
authors: M
authors: Lambert
authors: Pierre Emmanuel
authors: PE
authors: Morange
authors: Jean-Louis
authors: JL
authors: Bonnet
authors: Marie-Christine
authors: MC
authors: Alessi
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D004351:Drug Resistance; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D016015:Logistic Models; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010879:Piperazines / Q000009:adverse effects*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D013876:Thiophenes / Q000009:adverse effects*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: ACS; AUC; BARC; BMI; Bleeding Academic Research Consortium; CI; HR; HTPR; PCI; PRI VASP; ST-segment elevation myocardial infarction; STEMI; VLTPR; acute coronary syndromes; area under the receiver-operating curve; bleeding clopidogrel; body mass index; confidence interval; hazard ratio; high on-treatment platelet reactivity; percutaneous coronary intervention; platelet reactivity index vasodilator-stimulated phosphoprotein; platelet testing; prasugrel; very low on-treatment platelet reactivity