title: Pharmacodynamic comparison of pitavastatin versus atorvastatin on platelet reactivity in patients with coronary artery disease treated with dual antiplatelet therapy.
abstract: BACKGROUND
  Levels of platelet reactivity in patients on dual antiplatelet therapy (DAPT) can be influenced by concomitant treatment with statins. We verified if the pharmacodynamic effects of CYP3A4-metabolized statins (atorvastatin) and non-CYP3A4-metabolized statins (pitavastatin) differ in patients with coronary artery disease (CAD) treated with DAPT.
  
  
  RESULTS
  A total of 155 CAD patients receiving DAPT (clopidogrel 75mg plus aspirin 100mg) entered the PORTO trial. Patients were randomly assigned to atorvastatin (20mg day) or pitavastatin (4mg day) for 30 days, and then switched to the other drug for 30 days. Platelet reactivity was expressed as VerifyNow P2Y12 platelet response units (PRU) before and after each 30-day treatment period. High platelet reactivity was defined as PRU >208. As compared with pretreatment (192±49), PRU was significantly higher after 30-day atorvastatin (210±56; P=0.003), but was unchanged after 30-day pitavastatin (199±47 PRU, NS). In the 48 patients with PRU >208 at baseline (232±44), PRU increased significantly after 30-day atorvastatin (258±41, P=0.004), but not after 30-day pitavastatin (237±43, NS). In the 107 patients with PRU <208 at baseline (174±52), PRU did not change significantly with respect to baseline either after 30-day atorvastatin (188±61, NS) or after 30-day pitavastatin (181±59, NS).
  
  
  CONCLUSIONS
  Pitavastatin, a non-CYP3A4-metabolized statin, does not affect clopidogrel's response as compared with atorvastatin in patients who are borderline or poor responders to DAPT.
authors.affiliation: Department "Attilio Reale", Sapienza University.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pelliccia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rosano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marazzi
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vitale
authors.forename: Ilaria
authors.initials: I
authors.lastname: Spoletini
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Franzoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Speziale
authors.forename: Marina
authors.initials: M
authors.lastname: Polacco
authors.forename: Cesare
authors.initials: C
authors.lastname: Greco
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaudio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage*; D000069059:Atorvastatin; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000201:enzymology; D003430:Cross-Sectional Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D011804:Quinolines / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D011804:Quinolines; D000069059:Atorvastatin; D000077144:Clopidogrel; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C108475:pitavastatin; D013988:Ticlopidine; D001241:Aspirin