title: Uric acid and high-residual platelet reactivity in patients treated with clopidogrel or ticagrelor.
abstract: OBJECTIVE
  High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the past as a possible risk factor for coronary artery disease, with a possible association with platelets hyperreactivity. So far no studies have assessed the role of serum uric acid on the response to dual antiplatelet therapy. Therefore, the aim of our study was to evaluate the impact of uric acid levels on platelet function in patients treated with dual antiplatelet therapy (DAPT) with clopidogrel or ticagrelor.
  
  
  RESULTS
  We scheduled for platelet function assessment at 30-90 days post-discharge patients treated with DAPT (ASA + clopidogrel or ticagrelor) for an ACS or elective percutaneous coronary intervention (PCI). Platelet function was assessed by whole blood impedance aggregometry (Multiplate(®)-Roche Diagnostics AG), HRPR was considered for ASPI test >862 AU(∗)min (for ASA) and ADP test values ≥417 AU* min (for ADP-antagonists).
  
  
  RESULTS
  We included a total of 493 patients (262 were on ASA and clopidogrel and 231 on ASA and ticagrelor). Patients were divided according to quartiles of serum uric acid levels measured at the time of platelet aggregation assessment (Group 1 <4.6 mg/dL, n = 114; Group 2, 4.7-5.8 mg/dL, n = 133; Group 3, 5.9-6.8 mg/dL, n = 124; Group 4, >6.9, n = 122). Patients with higher uric acid levels were older, more often smokers, with history of hypertension and previous coronary artery bypass surgery and renal failure and were more often on therapy with diuretics at admission. Patients with higher SUA had higher triglycerides and fibrinogen. Uric acid levels did not influence ASPI, COL, TRAP and ADP tests. High residual platelet reactivity (HRPR) was observed in 1.5% of patients treated with ASA, with no difference according to SUA quartiles (p = 0.60), confirmed at multivariate analysis after correction for baseline confounders (adjusted OR[95%CI] = 1.05 [0.44-2.52], p = 0.90). HRPR for ADP-antagonists was observed in 23.6% of patients, with no difference according to SUA quartiles (p = 0.47); this result was confirmed also after correction for baseline confounders (adjusted OR[95%CI] = 1.04 [0.84-1.28], p = 0.73). Moreover, no association was found between HRPR and uric acid levels both among patients treated with clopidogrel (p = 0.35) or ticagrelor (p = 0.74), that was confirmed after correction for baseline confounding factors (adjusted OR[95%CI] = 1.18 [0.90-1.55], p = 0.23) and (adjusted OR[95%CI] = 0.96 [0.63-1.47], p = 0.85). The absence of association between SUA and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = 0.03, p = 0.55) or ticagrelor (r = -0.01, p = 0.85).
  
  
  CONCLUSIONS
  This is the first large study showing that in patients receiving DAPT, uric acid levels do not influence response to ticagrelor and clopidogrel or the effectiveness of ASA.
authors: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors: L
authors: L
authors: Barbieri
authors: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors: M
authors: M
authors: Verdoia
authors: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors: P
authors: P
authors: Pergolini
authors: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors: M
authors: M
authors: Nardin
authors: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors: R
authors: R
authors: Rolla
authors: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors: P
authors: P
authors: Marino
authors: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors: G
authors: G
authors: Bellomo
authors: Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands.
authors: H
authors: H
authors: Suryapranata
authors: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. Electronic address: giuseppe.deluca@maggioreosp.novara.it.
authors: G
authors: G
authors: De Luca
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D010979:Platelet Function Tests; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014280:Triglycerides; D014527:Uric Acid; D005340:Fibrinogen; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Antithrombotic therapy; Bleedings; Thrombosis; Uric acid