title: Parathyroid Hormone Levels and High-Residual Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy With Acetylsalicylic Acid and Clopidogrel or Ticagrelor.
abstract: BACKGROUND
  High-residual-on-treatment platelet reactivity still represents a challenging issue, potentially vanishing the benefits of dual antiplatelet treatment in patients with coronary artery disease. However, very few is known on the determinants of suboptimal response to antiplatelet agents. Recent interests have emerged on the potential prothrombotic effect of parathyroid hormone (PTH). Therefore, the aim of the present study was to assess the impact of parathyroid hormone (PTH) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI.
  
  
  METHODS
  Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30- to 90-days postdischarge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP antagonists).
  
  
  RESULTS
  We included 362 patients on DAPT, 125 (34.5%) receiving clopidogrel, and 237 (65.5%) on ticagrelor. Patients were divided according to PTH quartiles values (<45.8; 45.8-60.3; 60.4-88; ≥88.1 pg/mL). Higher PTH was associated with older age (P = 0.001); renal failure (P < 0.001), higher HDL cholesterol (P = 0.006) and creatinine (P < 0.001) and lower 25-OH cholecalciferol (P < 0.001). Suboptimal response to ASA was infrequent (2.8%), and not influenced by the levels of PTH (P = 0.57). ADP-mediated platelet aggregation was significantly increased in patients with higher PTH (P = 0.03), with an absolute increase in the prevalence of HRPR to ADP antagonists for higher PTH (24.7% vs. 40%, P = 0.007 for 4th vs. 1-3rd quartiles, adjusted OR[95%CI] = 2.04[1.14-3.64], P = 0.02). By the use of the ROC curve, we identified PTH levels above 96.7 pg/mL as the best predictor of HRPR with ADP antagonists (adjusted OR[95%CI] = 2.52[1.31-4.87], P = 0.006). Higher rate of HRPR was confirmed for PTH >96.7 pg/mL among the subgroup of patients on clopidogrel (51.5 vs. 85.7%, P = 0.001; adjusted OR[95%CI] = 12.5[2.6-60.9], P = 0.002), but not among ticagrelor-treated patients (11.3 vs. 16.7%, P = 0.31; adjusted OR[95%CI] = 1.55[0.56-4.6], P = 0.42).
  
  
  CONCLUSIONS
  In patients receiving dual antiplatelet therapy for coronary artery disease, higher PTH levels are associated with an increased ADP-mediated platelet reactivity and suboptimal response to clopidogrel, especially for values above 96.7 pg/mL, while not influencing the effectiveness of ASA and ticagrelor.
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Verdoia
authors.affiliation: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pergolini
authors.affiliation: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rolla
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Nardin
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Barbieri
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Alon
authors.initials: A
authors.lastname: Schaffer
authors.affiliation: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marino
authors.affiliation: Department of Cardiology, UMC St Radboud, Nijmegen, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000628:therapy*; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000244:Adenosine Diphosphate / Q000008:administration & dosage; D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy*; D016208:Databases, Factual; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D018398:Homeodomain Proteins / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014157:Transcription Factors / Q000097:blood*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C078492:HHEX protein, human; D018398:Homeodomain Proteins; D010975:Platelet Aggregation Inhibitors; D014157:Transcription Factors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
keywords: Clopidogrel; Dual antiplatelet therapy; High-residual platelet reactivity; Parathyroid hormone; Ticagrelor