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Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

BMJ 2011; 342 doi: (Published 11 May 2011) Cite this as: BMJ 2011;342:d2690
  1. Mette Charlot, research fellow1,
  2. Erik L Grove, research fellow2,
  3. Peter Riis Hansen, consultant cardiologist1,
  4. Jonas B Olesen, research fellow1,
  5. Ole Ahlehoff, research fellow1,
  6. Christian Selmer, research fellow1,
  7. Jesper Lindhardsen, research fellow1,
  8. Jan Kyst Madsen, head of department1,
  9. Lars Køber, professor of cardiology3,
  10. Christian Torp-Pedersen, professor of cardiology1,
  11. Gunnar H Gislason, consultant cardiologist1
  1. 1Department of Cardiology, Copenhagen University Hospital Gentofte, Post 635, Niels Andersens Vej 65, 2900 Hellerup, Denmark
  2. 2Department of Cardiology, Aarhus University Hospital Skejby, Aarhus, Denmark
  3. 3The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
  1. Correspondence to: M Charlot mc{at}
  • Accepted 15 March 2011


Objective To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction.

Design Retrospective nationwide propensity score matched study based on administrative data.

Setting All hospitals in Denmark.

Participants All aspirin treated patients surviving 30 days after a first myocardial infarction from 1997 to 2006, with follow-up for one year. Patients treated with clopidogrel were excluded.

Main outcome measures The risk of the combined end point of cardiovascular death, myocardial infarction, or stroke associated with use of proton pump inhibitors was analysed using Kaplan-Meier analysis, Cox proportional hazard models, and propensity score matched Cox proportional hazard models.

Results 3366 of 19 925 (16.9%) aspirin treated patients experienced recurrent myocardial infarction, stroke, or cardiovascular death. The hazard ratio for the combined end point in patients receiving proton pump inhibitors based on the time dependent Cox proportional hazard model was 1.46 (1.33 to 1.61; P<0.001) and for the propensity score matched model based on 8318 patients it was 1.61 (1.45 to 1.79; P<0.001). A sensitivity analysis showed no increase in risk related to use of H2 receptor blockers (1.04, 0.79 to 1.38; P=0.78).

Conclusion In aspirin treated patients with first time myocardial infarction, treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events.


  • Contributors: MC, ELG, PRH, CT-P, and GHG conceived and designed the study. All authors analysed and interpreted the data, critically revised the manuscript for important intellectual content, and provided administrative, technical, or material support. MC and GHG carried out the statistical analysis. MC drafted the manuscript. MC and CT-P obtained funding. MC, CT-P, and GHG had full access to the data and take full responsibility for its integrity.

  • Funding: This study was funded by the Danish Heart Foundation (10-04-R78-A2865-22586). The funding source had no influence on the study design, interpretation of results, or decision to submit the article.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare that (1) none haS company support for the submitted work; (2) the authors have no relationships with companies that might have an interest in the submitted work in the previous 3 years; (3) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) the authors have no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: This study was approved by the Danish Data Protection Agency (2007-41-1667) and data at the individual case level were made available by the national registers in anonymised form. Registry studies do not require ethical approval in Denmark.

  • Data sharing: No additional data available.

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