title: Proton pump inhibitors and the risk of adverse cardiac events.
abstract: BACKGROUND
  Recent evidence suggests that proton pump inhibitors (PPIs) might be linked with adverse cardiac events, but a causal relationship is unproven.
  
  
  METHODS
  We applied the self-matched case series method to two studies using population-based health care data from Ontario, Canada between 1996 and 2008. The first included subjects aged 66 years or older hospitalized for acute myocardial infarction within 12 weeks following initiation of PPI, while the second included subjects hospitalized for heart failure. In both studies we designated the primary risk interval as the initial 4 weeks of therapy and the control interval as the final 4 weeks. To test the specificity of our findings we examined use of histamine H2 receptor antagonists and benzodiazepines, drugs with no plausible causal link to adverse cardiac events.
  
  
  RESULTS
  During the 13-year study period, we identified 5550 hospital admissions for acute myocardial infarction and 6003 admissions for heart failure within 12 weeks of commencing PPI therapy. In the main analyses, we found that initiation of a PPI was associated with a higher risk of acute myocardial infarction (odds ratio 1.8; 95% confidence interval 1.7 to 1.9) and heart failure (odds ratio 1.8; 95% confidence interval 1.7 to 1.9). However, secondary analyses revealed similar risk estimates histamine H2 receptor antagonists and benzodiazepines, drugs with no known or suspected association with adverse cardiac events.
  
  
  CONCLUSIONS
  PPIs are associated with a short-term risk of adverse cardiac events, but similar associations are seen with other drugs exhibiting no known cardiac toxicity. Collectively these observations suggest that the association between PPIs and adverse cardiac events does not represent reflect cause-and-effect.
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada ; The Sunnybrook Research Institute, Toronto, Ontario, Canada ; Department of Medicine, University of Toronto, Toronto, Ontario, Canada ; Department of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Anjie
authors.initials: A
authors.lastname: Huang
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Hellings
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada ; Department of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada ; Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada ; Centre for Evaluation of Medicines, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
authors.affiliation: Manitoba Centre for Health Policy, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada ; The Winnipeg Regional Health Authority, Winnipeg, Manitoba, Canada.
authors.forename: Colette
authors.initials: C
authors.lastname: Raymond
authors.affiliation: Manitoba Centre for Health Policy, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada ; The Winnipeg Regional Health Authority, Winnipeg, Manitoba, Canada ; Women and Children's Research Institute and the Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Calgary, Alberta, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Kozyrskyj
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Yola
authors.initials: Y
authors.lastname: Moride
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Macdonald
authors.affiliation: The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada ; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada ; Department of Medicine, University of Toronto, Toronto, Ontario, Canada ; Department of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada ; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Mamdani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology* / Q000628:therapy; D006760:Hospitalization; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology* / Q000628:therapy; D009864:Ontario / Q000453:epidemiology; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D054328:Proton Pump Inhibitors