title: Impact of atorvastatin or rosuvastatin co-administration on platelet reactivity in patients treated with dual antiplatelet therapy.
abstract: BACKGROUND
  Residual high-on treatment platelet reactivity (HRPR) still represents a challenging matter in patients with coronary artery disease. Drug-to-drug interaction has been suggested between some statin and antiplatelet agents, despite their co-administration is mandatory in patients after an acute cardiovascular event or coronary stenting. Therefore, the aim of the current study was to investigate any impact of rosuvastatin or atorvastatin co-administration on platelet reactivity in patients receiving dual antiplatelet therapy (DAPT).
  
  
  METHODS
  Our population is represented by patients on DAPT (ASA and either clopidogrel 75 mg or ticagrelor 90 mg b.i.d) after an ACS or percutaneous revascularization, and receiving rosuvastatin or atorvastatin. Platelet function was assessed by Multiplate Impedance Aggregometry (Roche Diagnostics AG).
  
  
  RESULTS
  We included a total of 374 patients, 240 (64.2%) receiving atorvastatin, 134 (35.8%) rosuvastatin. Rosuvastatin treated patients were more often using beta-blockers (p = 0.05), diuretics (p = 0.04) and displayed higher HDL (p < 0.001) and lower LDL cholesterol (p < 0.001). The prevalence of HRPR for ASA was low, with no difference according to statin type (0.8% vs 1.5%, p = 0.62, adjusted OR[95%CI] = 2[0.23-16.6], p = 0.52). Concerning ADP-antagonists, in the 163 patients treated with clopidogrel, rosuvastatin co-administration was associated with a significantly increased rate of HRPR (55.6%vs 32%, p = 0.01, adjusted OR[95%CI] = 2.69[1.22-5.96], p = 0.015) with higher ADP-mediated platelet reactivity (p = 0.01) and TRAP-test results (p = 0.04). On the contrary, in the 211 ticagrelor treated patients, statin type did not affect mean platelet reactivity or the prevalence of HRPR with ticagrelor (10.5% vs 11.2%, p = 0.99, adjusted OR[95%CI] = 0.86[0.34-2.22], p = 0.76) CONCLUSIONS: Among patients receiving DAPT, rosuvastatin but not atorvastatin is associated with an increased rate of HRPR for clopidogrel, without any influence on the antiplatelet effect of ASA or ticagrelor. Therefore, cautiousness should be exerted for clopidogrel and rosuvastatin therapeutic association.
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Verdoia
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Nardin
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sartori
authors.affiliation: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pergolini
authors.affiliation: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rolla
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Barbieri
authors.affiliation: Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marino
authors.affiliation: Clinical Chemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
authors.affiliation: Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands.
authors.forename: Harry
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: Giuseppe
authors.initials: G
authors.lastname: De Luca
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D019338:Polypharmacy; D018570:Risk Assessment; D012307:Risk Factors; D000068718:Rosuvastatin Calcium / Q000009:adverse effects / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
keywords: Clopidogrel; Cythocromes; Rosuvastatin; Ticagrelor