title: Proton pump inhibitor use represents an independent risk factor for myocardial infarction.
abstract: BACKGROUND
  There is substantial debate regarding the development of acute coronary syndrome in patients using proton pump inhibitors (PPIs) combined with clopidogrel. However, data remain limited to address the effect of PPIs alone on the subsequent risk of myocardial infarction (MI). We aimed to explore the subsequent risk of MI in PPI users who had no previous history of MI.
  
  
  METHODS
  The records of inpatients and outpatients with PPI prescriptions were retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2009. We conducted two different study designs, the first using propensity score (PS)-matching analyses and the second using case-crossover analyses. The risk of developing MI for PPI users was analyzed in the PS-matched study. The association between risk of MI and prior PPI exposure was further validated in the case-crossover study.
  
  
  RESULTS
  In the PS-matched study, we included 126,367 PPI users and 126,367 PS-matched PPI non-users. After 120 days of follow-up, PPI use was associated with a 1.58-fold greater risk of MI (adjusted hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.11 to 2.25). In the case-crossover study, adjusted odds ratios of PPI for MI risk were 4.61 (95% CI = 1.76 to 12.07) for the 7-day window and 3.47 (95% CI = 1.76 to 6.83) for the 14-day window.
  
  
  CONCLUSIONS
  Use of PPIs may be independently associated with an increased risk of MI. However, the benefits of PPIs may greatly outweigh the risks of adverse cardiovascular effects, with number needed to harm of 4357.
authors.affiliation: Department of Medicine, Taipei Veterans General Hospital, Yuanshan Branch, Yilan, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Shih
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medicine, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan.
authors.forename: Yung-Tai
authors.initials: YT
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shuo-Ming
authors.initials: SM
authors.lastname: Ou
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Szu-Yuan
authors.initials: SY
authors.lastname: Li
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzeng-Ji
authors.initials: TJ
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: sjwang@vghtpe.gov.tw.
authors.forename: Shuu-Jiun
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D057216:Propensity Score; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors
keywords: Epidemiology; Myocardial infarction; Proton pump inhibitors