title: Advanced age and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor.
abstract: ESSENTIALS: Dual antiplatelet therapy (DAPT) in elderly patients requires balancing bleedings and thrombosis. Impact of age on high residual on-treatment platelet reactivity (HRPR) on DAPT was studied. A reduced effectiveness of adenosine diphosphate antagonists was observed over 70 years of age. The occurrence of HRPR was increased among elderly patients with both clopidogrel and ticagrelor.
  
  
  BACKGROUND
  The aim of the present study was to evaluate the impact of age on platelet function and the occurrence of high residual on-treatment platelet reactivity (HRPR) in patients treated with dual antiplatelet therapy (DAPT) using acetylsalicilic acid (ASA) and clopidogrel or ticagrelor.
  
  
  METHODS
  Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test values > 862 AU*min (for ASA) and adenosine diphosphate (ADP) test values > 417 AU*min (for ADP antagonists). Elderly patients were defined as those aged ≥ 70 years.
  
  
  RESULTS
  Among 494 patients on DAPT, 224 (45.3%) were ≥ 70 years old. ADP-mediated platelet aggregation increased with decades of age (279.3 ± 148.6 vs. 319.6 ± 171.1 vs. 347.3 ± 190.1 vs. 345.7 ± 169.2), whereas no difference was observed for ASA response. A reduced effectiveness of ADP antagonists was observed among elderly patients; in fact, among the 117 patients displaying HRPR (23.7%), a higher prevalence was observed among patients over 70 years old (30.4% vs. 18.1%; adjusted odds ratio (OR) [95% confidence interval (CI)] = 2.19 [1.29-3.71]). Similar results were obtained among the 266 clopidogrel-treated patients (38.5% vs. 27.9%; adjusted OR [95% CI] = 2.91 [1.46-5.8]) and in the 228 patients receiving ticagrelor (19.1% vs. 8.1%; adjusted OR [95% CI] = 2.55 [1.02-8.59]).
  
  
  CONCLUSIONS
  In patients receiving dual antiplatelet therapy, advanced age is independently associated with a reduced effectiveness of ADP antagonists and a higher rate of HRPR with both clopidogrel and ticagrelor.
authors.affiliation: Department of Cardiology, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Verdoia
authors.affiliation: Clinical Chemistry, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pergolini
authors.affiliation: Clinical Chemistry, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rolla
authors.affiliation: Department of Cardiology, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Nardin
authors.affiliation: Department of Cardiology, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Schaffer
authors.affiliation: Department of Cardiology, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Barbieri
authors.affiliation: Department of Cardiology, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Marino
authors.affiliation: Clinical Chemistry, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bellomo
authors.affiliation: Cardiology, UMC St Radboud, Nijmegen, the Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: Department of Cardiology, Ospedale 'Maggiore della Carità', Eastern Piedmont University, Novara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Luca
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000244:Adenosine Diphosphate / Q000378:metabolism; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010351:Patient Discharge; D062645:Percutaneous Coronary Intervention; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D015995:Prevalence; D013927:Thrombosis / Q000188:drug therapy; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
keywords: aging; antithrombotic agents; coronary artery disease; pharmacology; platelet aggregation inhibitors