title: Platelet inhibitory effect of clopidogrel in patients treated with omeprazole, pantoprazole, and famotidine: a prospective, randomized, crossover study.
abstract: BACKGROUND
  Concerns about an inhibitory effect of proton pump inhibitors (PPIs) on clopidogrel metabolism have been raised. Because the pharmacological effect of clopidogrel is dependent on genetically determined activity of the hepatic cytochrome P450 isoenzymes system, it is important to examine the interaction between different PPIs and high on-treatment platelet reactivity (HPR) after controlling for genetic variability. The aim of the study was to assess the effect of 2 PPIs and a histamine-2 (H2) receptor-blocker on platelet reactivity in a crossover trial where each patient was alternately treated with each drug.
  
  
  OBJECTIVE
  Omeprazole reduces HPR more than other PPI or H2 blockers.
  
  
  METHODS
  Patients treated with aspirin and clopidogrel for at least 1 month were assigned to 3 consecutive 1-month treatment periods during which they were treated with each of the 3 study medications twice daily: omeprazole 20 mg, famotidine 40 mg, and pantoprazole 20 mg. At the end of each treatment phase, platelet function was evaluated with the Verify Now system using 2 cutoff values (>208 P2Y12 reaction units [PRUs] and >230 PRUs) for the definition of HPR.
  
  
  RESULTS
  Patients with HPR were older than those without HPR (62 ± 10 vs 55 ± 8 years, respectively, P = 0.03). HPR was more prevalent during omeprazole therapy compared to famotidine or pantoprazole (48%, 33%, and 31%, respectively, for the 208 PRU cutoff, P= 0.04; and 37%, 17%, and 23%, respectively, for the 230 PRU cutoff, P= 0.003).
  
  
  CONCLUSIONS
  After eliminating the effects of interindividual variability in clopidogrel metabolism, omeprazole therapy was associated with substantially more HPR than famotidine or pantoprazole.
authors: Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Yaron
authors: Y
authors: Arbel
authors: Edo Y
authors: EY
authors: Birati
authors: Ariel
authors: A
authors: Finkelstein
authors: Amir
authors: A
authors: Halkin
authors: Hanna
authors: H
authors: Kletzel
authors: Yigal
authors: Y
authors: Abramowitz
authors: Shlomo
authors: S
authors: Berliner
authors: Varda
authors: V
authors: Deutsch
authors: Itzhak
authors: I
authors: Herz
authors: Gad
authors: G
authors: Keren
authors: Shmuel
authors: S
authors: Banai
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004347:Drug Interactions; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D015738:Famotidine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007557:Israel; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000009:adverse effects / Q000627:therapeutic use*; D000077402:Pantoprazole; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D006635:Histamine H2 Antagonists; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D015738:Famotidine; D000077144:Clopidogrel; D000077402:Pantoprazole; D009853:Omeprazole; D013988:Ticlopidine; D001241:Aspirin
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