No Increase in Risk of Acute Myocardial Infarction in Privately Insured Adults Prescribed Proton Pump Inhibitors vs Histamine-2 Receptor Antagonists (2002–2014)

  • Suzanne N. Landi
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Robert S. Sandler
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

    Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
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  • Virginia Pate
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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  • Jennifer L. Lund
    Reprint requests Address requests for reprints to: Jennifer Lund, PhD, 2102D McGavran-Greenberg Hall, CB #7435,135 Dauer Drive, Chapel Hill, North Carolina 27599-7435. fax: (919) 966–7440.
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Published:November 06, 2017DOI:

      Background & Aims

      Proton pump inhibitors (PPIs) are commonly used medications. Recent studies reported an increased risk of acute myocardial infarction (MI) in PPI users vs non-users. We evaluated MI risk associated with PPIs compared with histamine-2 receptor antagonists (H2RAs) in privately insured adults in the United States.


      Using administrative claims from commercial and Medicare Supplemental plans (2001–2014), we compared risk of MI in patients who started a new prescription for PPIs vs H2RAs. Enrollees were followed from their first prescription until MI, medication discontinuation, plan disenrollment, or December 31, 2014. MI was defined using hospital diagnosis codes. Risk differences (RD), risk ratios, and 95% confidence intervals (CIs) were estimated using Kaplan-Meier methods at 3, 12, and 36 months after treatment initiation. Standardized morbidity ratio weights were used to control measured confounding. Analyses were stratified by plan type (commercial vs Medicare Supplemental).


      We identified more than 5 million new users of prescription PPIs and H2RAs. Median follow-up time was 60 days for patients with commercial insurance and 96 days in patients with Medicare Supplemental insurance. The 12-month weighted risk of MI was low overall (approximately 2 cases per 1000 among patients in commercial plans; 8 per 1000 among patients in Medicare Supplemental plans). In the RD analysis, we found no significant differences in MI risk between patients who started PPIs vs H2RAs for the first 12 months, either in the commercial population (weighted RD per 1000, –0.08; 95% CI, –0.51 to 0.36) or the Medicare Supplemental population (weighted RD per 1000, –0.45; 95% CI, –1.53 to 0.58).


      In an analysis of administrative claims from commercial and Medicare Supplemental plans, we found no evidence that prescription PPIs increase risk of MI compared with prescription H2RAs. Physicians and patients should not avoid starting a PPI because of concerns related to MI risk.

      Graphical abstract


      Abbreviations used in this paper:

      ADMA (asymmetrical dimethylarginine), CI (confidence interval), FDAs (Food and Drug Administration), GERD (gastroesophageal reflux disease), H2RA (histamine-2 receptor antagonists), ICD-9-CM (International Classification of Diseases), Ninth Revision (Clinical Modification), IQR (interquartile range), MI (myocardial infarction), PPI (proton pump inhibitor), PS (propensity score), RD (risk difference), RR (risk ratio), SMR (standardized morbidity ratio)
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