Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) registry

Circulation. 2011 Feb 8;123(5):474-82. doi: 10.1161/CIRCULATIONAHA.110.965640. Epub 2011 Jan 24.


Background: Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs.

Methods and results: The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively.

Conclusion: PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles.

Trial registration: NCT00673036.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Clopidogrel
  • Cohort Studies
  • Cytochrome P-450 CYP2C19
  • Drug Therapy, Combination
  • Female
  • France / epidemiology
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / complications
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / mortality
  • Platelet Aggregation Inhibitors / therapeutic use
  • Proton Pump Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Registries
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine

Associated data