title: Impact of pentoxifylline on platelet function profiles in patients with type 2 diabetes mellitus and coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel.
abstract: OBJECTIVE
  The aim of this study was to evaluate the impact of the phosphodiesterase (PDE) inhibitor pentoxifylline on platelet function profiles in patients receiving dual antiplatelet therapy (DAPT).
  
  
  BACKGROUND
  Previous studies have shown that, in patients receiving DAPT, the adjunctive use of a PDE inhibitor enhances platelet inhibition, particularly in those presenting with diabetes mellitus (DM). However, the pharmacodynamic (PD) effects of the PDE inhibitor pentoxifylline on platelet function profiles in DM patients receiving DAPT are unknown.
  
  
  METHODS
  This was a prospective, randomized, double-blind, parallel design study conducted in DM patients with stable coronary artery disease receiving DAPT. Patients were randomly assigned to either pentoxifylline 400 mg or placebo 3 times daily for 14 days. The PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetric, Inc., San Diego, California), and multiple electrode aggregometry at baseline and 14 days. The PD effects were also assessed according the presence or absence of high on-treatment platelet reactivity status.
  
  
  RESULTS
  A total of 40 patients were available for analysis. At 14 days, there were no differences in the P2Y(12) reactivity index as assessed by vasodilator-stimulated phosphoprotein phosphorylation between treatment groups (primary endpoint; p = 0.93). Intra-group comparisons also failed to show any differences between baseline and 14-day P2Y(12) reactivity index assessment in the placebo and pentoxifylline arms (p = 0.61). There were no significant inter- and intra-group differences in all other PD measures. The PD effects did not vary according the presence or absence of high on-treatment platelet reactivity.
  
  
  CONCLUSIONS
  Adjunctive treatment with pentoxifylline is not associated with increased platelet inhibitory effects in DM patients with coronary artery disease receiving DAPT.
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida 32209, USA.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ueno
authors.forename: José L
authors.initials: JL
authors.lastname: Ferreiro
authors.forename: Salvatore D
authors.initials: SD
authors.lastname: Tomasello
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Davide
authors.initials: D
authors.lastname: Capodanno
authors.forename: Naveen
authors.initials: N
authors.lastname: Seecheran
authors.forename: Murali
authors.initials: M
authors.lastname: Kodali
authors.forename: Kodlipet
authors.initials: K
authors.lastname: Dharmashankar
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Charlton
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005431:Florida; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010726:Phosphodiesterase Inhibitors; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D010431:Pentoxifylline