title: Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study.
abstract: OBJECTIVE
  The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction.
  
  
  RESULTS
  In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline]. The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (-53.6±48.4% versus +0.8±53.7% without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (-81.8 %±24.8% vs. -72.9%±32.9% without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups.
  
  
  CONCLUSIONS
  The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.
authors.affiliation: ACTION Study Group, Hôpital Pitié-Salpêtrière (APHP), Institut de Cardiologie, INSERM, UMR_S 1166, Pitié-Salpêtrière Hospital (AP-HP), Université Pierre et Marie Curie (UPMC Paris 6), 75013, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Jérémie
authors.initials: J
authors.lastname: Abtan
authors.forename: Ghalia
authors.initials: G
authors.lastname: Anzaha
authors.forename: Mathieu
authors.initials: M
authors.lastname: Kerneis
authors.forename: Johanne
authors.initials: J
authors.lastname: Silvain
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cayla
authors.forename: Stephen A
authors.initials: SA
authors.lastname: O'Connor
authors.forename: Olivier
authors.initials: O
authors.lastname: Barthélémy
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
authors.forename: Sophie
authors.initials: S
authors.lastname: Galier
authors.forename: Delphine
authors.initials: D
authors.lastname: Brugier
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stanek
authors.forename: Scott L
authors.initials: SL
authors.lastname: Charland
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gallois
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
mesh_terms: D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D064747:Lansoprazole / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000897:Anti-Ulcer Agents; C548576:P2RY12 protein, human; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D064747:Lansoprazole; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin