Effect of individual proton pump inhibitors on cardiovascular events in patients treated with clopidogrel following coronary stenting: results from the Ibaraki Cardiac Assessment Study Registry

Catheter Cardiovasc Interv. 2012 Oct 1;80(4):556-63. doi: 10.1002/ccd.23327. Epub 2012 Jan 10.


Objectives: The aim of this study was to evaluate whether combination therapy of clopidogrel and proton pump inhibitors (PPIs) causes higher numbers of cardiovascular events than clopidogrel alone in Japanese patients.

Background: PPIs are often prescribed in combination with clopidogrel following coronary stenting. PPIs are reported to diminish the effect of clopidogrel because both are metabolized by CYP2C19. However, no reports address the effects of PPIs on cardiovascular events following coronary stenting in the Japanese population.

Methods: A total of 1,887 patients treated with clopidogrel following coronary stenting were enrolled in the Ibaraki Cardiac Assessment Study (ICAS) registry. All subjects were classified into two groups according to treatment without (n = 819) or with (n = 1,068) PPI. Propensity score analysis matched 1:1 according to treatment without PPI (n = 500) or with PPI (n = 500). Primary endpoint was the composite of all-cause death or myocardial infarction.

Results: No significant difference was observed in the primary endpoint between the group without PPI and the group with PPI (4.6% vs. 4.6%, P = 0.77). In contrast, a significant difference was found between the group without PPI and with PPI in regard to the incidence of gastrointestinal bleeding at the end of the follow-up period and the specific PPI prescribed (2.4% vs. 0.8%, adjusted HR = 0.30, 95% Confidence interval 0.08-0.87, P = 0.026) after propensity score matching.

Conclusions: No significant association between PPI use and primary endpoint was observed in the Japanese population, whereas PPI use resulted in a significant reduction in the rate of gastrointestinal bleeding.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Chi-Square Distribution
  • Clopidogrel
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Drug Interactions
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / mortality
  • Gastrointestinal Hemorrhage / prevention & control*
  • Humans
  • Incidence
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control*
  • Percutaneous Coronary Intervention / adverse effects
  • Percutaneous Coronary Intervention / instrumentation*
  • Percutaneous Coronary Intervention / mortality
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Propensity Score
  • Proportional Hazards Models
  • Proton Pump Inhibitors / therapeutic use*
  • Registries
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Stents*
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Ticlopidine