title: Effect of omeprazole on the concentration of interleukin-6 and transforming growth factor-β1 in patients receiving dual antiplatelet therapy after percutaneous coronary intervention.
abstract: BACKGROUND
  Dual antiplatelet therapy (aspirin plus clopidogrel) is recommended in patients undergoing percutaneous coronary intervention (PCI). Treatment with proton pump inhibitors (PPIs) decreases bleeding rate. Alarming reports have been made that PPIs may decrease the antiplatelet activity of clopidogrel. We sought to determine whether levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) might help distinguish individuals at risk for adverse events.
  
  
  METHODS
  Thirty-eight patients on aspirin and clopidogrel were enrolled and divided into two groups: group 1 [patients receiving omeprazole (n = 18)] and group 2 [patients not receiving omeprazole (n = 20)]. Patients underwent PCI and were scheduled for twelve-month clinical follow-up. The major, adverse cardiac and cerebrovascular events (MACCE) include death, re-hospitalization for acute coronary syndromes, and stroke.
  
  
  RESULTS
  Median concentrations of IL-6 were higher in group 1 at 4.7 pg/mL, in comparison with group 2, 1.65 pg/mL (p = 0.003). Median concentrations of TGF-β1 were similar in both groups (p = 0.5). Patients in group 1 had a significantly higher leukocyte count [103/mm3] (median 7.5 vs 6.5; p = 0.04). There were no deaths during follow-up. The incidence of myocardial infarction was higher in group 1 (33.4% vs 5.0%; p = 0.03). MACCE at twelve months were more frequent in group 1 (55.6% vs 20.0%; p = 0.02). The cut-off value to predict MACCEs for IL-6 was > 3.6 pg/mL (sensitivity 64%, specificity 88%, positive predictive value 75%, negative predictive value 81%).
  
  
  CONCLUSIONS
  We show here that concomitant omeprazole use is associated with an increased inflammatory reaction. Drug interactions may reduce the anti-inflammatory effect of clopidogrel. This mechanism maybe responsible for an increased risk of non-fatal, cardiovascular events, following stent placement.
authors.affiliation: 3rd Department of Cardiology, Silesian Center for Heart Disease, Medical University of Silesia, Zabrze, Poland. bartekh@mp.pl
authors.forename: Bartosz
authors.initials: B
authors.lastname: Hudzik
authors.forename: Janusz
authors.initials: J
authors.lastname: Szkodzinski
authors.forename: Aleksander
authors.initials: A
authors.lastname: Danikiewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wilczek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Romanowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lekston
authors.forename: Lech
authors.initials: L
authors.lastname: Polonski
authors.forename: Barbara
authors.initials: B
authors.lastname: Zubelewicz-Szkodzinska
mesh_terms: D000368:Aged; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D000077144:Clopidogrel; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000897:Anti-Ulcer Agents; D015415:Biomarkers; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D053773:Transforming Growth Factor beta1; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine; D001241:Aspirin