Proton pump inhibitor use was not associated with an increased risk of 1-year MI, stroke, or death in patients receiving clopidogrel for recent MI (HR 0.98; 95% CI 0.90-1.08; P=0.72).
Cohort (n=3,670)
Yes
Does proton pump inhibitor coadministration with clopidogrel increase the risk of cardiovascular events or mortality in patients with recent acute myocardial infarction?
Coadministration of PPIs with clopidogrel in patients with recent MI does not increase the risk of cardiovascular events or mortality, regardless of CYP2C19 genotype.
Effect estimate: HR 0.98 (95% CI 0.90 to 1.08)
p-value: p=0.72
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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00673036.
Simon et al. (Tue,) conducted a cohort in Acute Myocardial Infarction (n=3,670). Proton pump inhibitors (PPIs) and clopidogrel vs. No PPIs was evaluated on 1-year MI, stroke, or death (HR 0.98, 95% CI 0.90 to 1.08, p=0.72). Proton pump inhibitor use was not associated with an increased risk of 1-year MI, stroke, or death in patients receiving clopidogrel for recent MI (HR 0.98; 95% CI 0.90-1.08; P=0.72).