Authors
Simon T, Steg PG, Gilard M, et al.
Title
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-STElevation Myocardial Infarction (FAST-MI) registry
References
Circulation 2011;123:474-82
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.
Purpose
To assess the clinical impact of PPI treatment on the efficacy of clopidogrel therapy, with specific focus on CYP2C19 genetic polymorphisms
Design
  • 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.
Exclusion Criteria
  • Iatrogenic MI
  • Invalidation of the diagnosis of definite MI in favour of an alternative
  • unstable angina with no elevation of cardiac necrosis biomarkers
Follow-Up
1 year
Treatment Regimen
Clopidogrel with versus without PPI
Results
Primary Endpoints:
  • PPI treatment was not an independent predictor of 1-year survival (HR 0.97; 95% CI 0.87 to 1.08; P=0.57)
  • PI treatment was not an independent predictor of 1-year 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.

Secondary Endpoints:

  • In the propensity-matched cohorts, the OR 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.
  • In the propensity-matched cohorts, 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.
Summary
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.
Implications
Further data is needed on PPI use, loss-of-function alleles and risk of cardiovascular events.
Related Figures
None.