title: Platelet reactivity in patients with impaired renal function receiving dual antiplatelet therapy with clopidogrel or ticagrelor.
abstract: BACKGROUND
  Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only few studies have assessed the role of CKD on response to dual antiplatelet therapy (DAPT) with conflicting results. Therefore, the aim of our study was to evaluate the impact of CKD on platelet function in patients treated with DAPT after a recent acute coronary syndrome (ACS) or PCI.
  
  
  METHODS
  Patients treated with DAPT, acetylsalicylic acid (ASA)+adenosine diphosphate antagonist (ADP-antagonist) such as clopidogrel or ticagrelor, for ACS or elective patients undergoing PCI were scheduled for platelet function assessment at 30-90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®- Roche Diagnostics AG), high residual platelet reactivity (HRPR) was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists). Chronic renal failure was defined as an estimated glomerular filtration rate of 60 mol/min/1.73 m(2) or less, calculated by applying MDRD (Modification of Diet in renal Disease) formula.
  
  
  RESULTS
  Our population included a total of 537 patients of which 308 (57.3%) received ASA and clopidogrel and 229 (42.6%) received ASA and ticagrelor. Patients with renal failure at baseline (101 out of 537, 18.8%) were older, with higher prevalence of hypertension, previous myocardial infarction and coronary artery bypass graft surgery. Moreover, they had a lower ejection fraction at baseline and were more often in therapy with diuretics, but less often with statins at admission. They had lower haemoglobin and higher glycated haemoglobin. HRPR was observed in 1.5% of patients treated with ASA with no difference according to renal function (p=0.18). HRPR for ADP-antagonists was observed in 23.7% of patients, with no difference according to renal function (p=0.50). This result was confirmed either with clopidogrel (31.9% versus 38%, p=0.41) and ticagrelor (13.1% versus 10.8%, p=0.99), also after correction for all baseline confounders (clopidogrel: adjusted OR[95%CI]=1.26 [0.60-2.63], p=0.54) (ticagrelor: adjusted OR[95%CI]=0.95 [0.54-1.65], p=0.84). The absence of association between renal function and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r=-0.04, p=0.52) and ticagrelor (r=0.006, p=0.92).
  
  
  CONCLUSIONS
  In patients receiving DAPT, chronic renal failure did not influence ADP-mediated platelet reactivity, with both ticagrelor or clopidogrel. No influence of chronic renal failure was found on the effectiveness of ASA.
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: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pergolini
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: 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: Paolo
authors.initials: P
authors.lastname: Marino
authors.affiliation: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
authors.affiliation: 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. Electronic address: giuseppe.deluca@maggioreosp.novara.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000639:trends; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine