title: Serum uric acid levels during dual antiplatelet therapy with ticagrelor or clopidogrel: Results from a single-centre study.
abstract: New antithrombotic therapies have significantly improved the outcomes of patients with acute coronary syndrome (ACS), where the introduction of ticagrelor has provided the greatest mortality benefits. However, ticagrelor treatment has been associated with a potential increase in the serum uric acid (SUA) levels, which may influence endothelial dysfunction and prothrombotic status, thereby affecting the risk of acute cardiovascular events in patients requiring dual antiplatelet therapy (DAPT). The present study aimed to compare the impact of antiplatelet agents such as ticagrelor or clopidogrel on SUA levels and their effect on platelet reactivity.
  
  
  
  We included patients admitted for ACS or elective percutaneous coronary intervention (PCI) and discharged with ASA (acetylsalicylic acid; 100-160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day). Chemistry was assessed at admission (baseline) and after a 30-90-day period of DAPT (together with platelet reactivity). The absolute and percentage variations of SUA after DAPT introduction were considered. Multiple-electrode aggregometry was used to assess platelet function. A total of 378 patients were enrolled, with 145 treated with aspirin and clopidogrel (AC) and 233 with aspirin and ticagrelor (AT). The AC patients were older (p = 0.003) and more often showed elective PCI as an indication to DAPT (<0.001); they received chronic therapy with ARB (angiotensin II receptor blocker; p = 0.001), nitrates (p = 0.044), CCB (calcium channel blocker; p = 0.005) and diuretics (p = 0.044). The AT patients displayed a higher percentage of ACS diagnosis (p < 0.001) and received chronic therapy with ACE (angiotensin-converting enzyme) inhibitors (p = 0.001), beta blockers (p = 0.001) and statins (p = 0.013). The AC patients displayed higher platelet reactivity at COL (collagen) test, ASPI test and ADP (adenosine diphosphate) test (p = 0.03, 0.001 and <0.001, respectively) and a higher percentage of HRPR (high residual platelet reactivity) in the ADP test (p = 0.001). No difference was found in the baseline uric acid and creatinine levels between AC and AT patients. At 30-90 days, a significant absolute and percentage increase in the SUA levels was found in AT as compared to AC patients (0.204 mg/dl vs. -0.165 mg/dl, p = 0.034; 6.26% vs. -0.005%, p = 0.018, respectively). Results were not influenced by variations in renal function. At multivariate analysis, in fact, ticagrelor therapy emerged as an independent predictor of increase in the uric acid levels (odds ratio (OR; 95% confidence interval (CI)) = 2.79 (1.66-4.67), p < 0.001). However, the variation in the SUA levels did not affect platelet reactivity or HRPR in both AC and AT patients.
  
  
  
  An increase in the SUA levels at 30-90 days was observed in patients receiving chronic DAPT with ticagrelor, but not clopidogrel treatment. However, the changes in the SUA levels do not influence platelet aggregation.
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Nardin
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Verdoia
authors.affiliation: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pergolini
authors.affiliation: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rolla
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Barbieri
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Schaffer
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Marino
authors.affiliation: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bellomo
authors.affiliation: Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. Electronic address: giuseppe.deluca@maggioreosp.novara.it.
authors.forename: G
authors.initials: G
authors.lastname: De Luca
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; 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; D016896:Treatment Outcome; D015854:Up-Regulation; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D014527:Uric Acid; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
keywords: Clopidogrel; Platelet aggregation; Serum uric acid; Ticagrelor