Effect of omeprazole on the concentration of interleukin-6 and transforming growth factor-β1 in patients receiving dual antiplatelet therapy after percutaneous coronary intervention

Eur Cytokine Netw. 2010 Dec;21(4):257-63. doi: 10.1684/ecn.2010.0213. Epub 2010 Nov 18.


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%).

Interpretation: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Anti-Ulcer Agents / adverse effects
  • Anti-Ulcer Agents / pharmacology*
  • Anti-Ulcer Agents / therapeutic use
  • Aspirin / therapeutic use
  • Biomarkers / blood*
  • Clopidogrel
  • Coronary Angiography
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Omeprazole / adverse effects
  • Omeprazole / pharmacology*
  • Omeprazole / therapeutic use
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Predictive Value of Tests
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Transforming Growth Factor beta1 / blood*
  • Treatment Outcome


  • Anti-Ulcer Agents
  • Biomarkers
  • Interleukin-6
  • Platelet Aggregation Inhibitors
  • Transforming Growth Factor beta1
  • Clopidogrel
  • Omeprazole
  • Ticlopidine
  • Aspirin