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Research

Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study

BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i4857 (Published 28 September 2016) Cite this as: BMJ 2016;354:i4857

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该文章的中文翻译
  1. Andrea Arfè, biostatistician1,
  2. Lorenza Scotti, biostatistician1,
  3. Cristina Varas-Lorenzo, epidemiologist2,
  4. Federica Nicotra, biostatistician1,
  5. Antonella Zambon, biostatistician1,
  6. Bianca Kollhorst, biostatistician3,
  7. Tania Schink, biostatistician3,
  8. Edeltraut Garbe, pharmacoepidemiologist3,
  9. Ron Herings, pharmacoepidemiologist4,
  10. Huub Straatman, biostatistician4,
  11. René Schade, epidemiologist5,
  12. Marco Villa, epidemiologist6,
  13. Silvia Lucchi, biostatistician6,
  14. Vera Valkhoff, epidemiologist5,
  15. Silvana Romio, biostatistician5,
  16. Frantz Thiessard, medical computer scientist7,
  17. Martijn Schuemie, medical computer scientist5,
  18. Antoine Pariente, pharmacoepidemiologist7,
  19. Miriam Sturkenboom, pharmacoepidemiologist5,
  20. Giovanni Corrao, biostatistician1
  21. On behalf of the Safety of Non-steroidal Anti-inflammatory Drugs (SOS) Project Consortium
  1. 1Unit of Biostatistics, Epidemiology, and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, 20126 Milan, Italy
  2. 2RTI Health Solutions, Barcelona, Spain
  3. 3Leibniz Institute of Prevention Research and Epidemiology, Bremen, Germany
  4. 4PHARMO Institute, Utrecht, Netherlands
  5. 5Department of Medical Informatics, Erasmus University Medical Centre, Rotterdam, Netherlands
  6. 6Local Health Authority ASL Cremona, Cremona, Italy
  7. 7University of Bordeaux Segalen, Bordeaux, France
  1. Correspondence to: G Corrao giovanni.corrao{at}unimib.it
  • Accepted 1 September 2016

Abstract

Objectives To investigate the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs.

Design Nested case-control study.

Setting Five population based healthcare databases from four European countries (the Netherlands, Italy, Germany, and the United Kingdom).

Participants Adult individuals (age ≥18 years) who started NSAID treatment in 2000-10. Overall, 92 163 hospital admissions for heart failure were identified and matched with 8 246 403 controls (matched via risk set sampling according to age, sex, year of cohort entry).

Main outcome measure Association between risk of hospital admission for heart failure and use of 27 individual NSAIDs, including 23 traditional NSAIDs and four selective COX 2 inhibitors. Associations were assessed by multivariable conditional logistic regression models. The dose-response relation between NSAID use and heart failure risk was also assessed.

Results Current use of any NSAID (use in preceding 14 days) was found to be associated with a 19% increase of risk of hospital admission for heart failure (adjusted odds ratio 1.19; 95% confidence interval 1.17 to 1.22), compared with past use of any NSAIDs (use >183 days in the past). Risk of admission for heart failure increased for seven traditional NSAIDs (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and two COX 2 inhibitors (etoricoxib and rofecoxib). Odds ratios ranged from 1.16 (95% confidence interval 1.07 to 1.27) for naproxen to 1.83 (1.66 to 2.02) for ketorolac. Risk of heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib used at very high doses (≥2 defined daily dose equivalents), although some confidence intervals were wide. Even medium doses (0.9-1.2 defined daily dose equivalents) of indomethacin and etoricoxib were associated with increased risk. There was no evidence that celecoxib increased the risk of admission for heart failure at commonly used doses.

Conclusions The risk of hospital admission for heart failure associated with current use of NSAIDs appears to vary between individual NSAIDs, and this effect is dose dependent. This risk is associated with the use of a large number of individual NSAIDs reported by this study, which could help to inform both clinicians and health regulators.

Footnotes

  • We thank all members of the Safety of Non-steroidal Anti-inflammatory Drugs (SOS) Project Consortium for their collaborative efforts.

  • Contributors: All authors were members of the SOS Project Consortium. AA, LS, FN, AZ, BK, TS, HS, SL, and RS were involved in data management and statistical analysis. FT, AP, and MaS were responsible for the data harmonisation procedure and data preparation. CV-L, RH, MV, VV, and SR helped to interpret the findings and manage the study. MiS was the principal investigator of the SOS Project. AA, LS, FN, AZ, and GC (guarantors) drafted the manuscript. All listed authors helped revise the final manuscript.

  • Funding: The research leading to the results of this study received funding from the European Community’s seventh Framework Programme (grant agreement no 223495—the SOS Project). The funding source did not play any role in planning and implementing this study, in interpreting its results, and in writing this paper.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: GC collaborated with the advisory boards of Novartis and Roche and participated in projects funded by GlaxoSmithKline (GSK). HS and RH are employees of the PHARMO Institute, an independent research institute that performs financially supported studies for the government and related healthcare authorities and several pharmaceutical companies in the European Union. BK and TS work in departments that occasionally perform studies for the pharmaceutical companies, including Bayer-Schering, Celgene, GSK, Mundipharma, Novartis, Purdue, Sanofi-Aventis, Sanofi-Pasteur, Stada, and Takeda. EG runs a department that occasionally performs studies for pharmaceutical industries, including Bayer, Celgene, GSK, Mundipharma, Novartis, Sanofi, Sanofi Pasteur MSD, and STADA; has been a consultant to Bayer, Nycomed, Teva, GSK, Schwabe, and Novartis (the SOS Project was not funded or cofunded by any of these companies). SL and MV, as employees of the local health authority of Cremona, have perfomed research studies sponsored by pharmaceutical companies (Pfizer Italia, GSK, and Novartis V&D) unrelated to this study. CV-L, as an employee of RTI Health Solutions, worked on projects funded by pharmaceutical companies including manufacturers of treatments for pain and inflammation; and participates in advisory boards funded by pharmaceutical companies. MaS has, since completion of this research, accepted a full time position at Janssen R&D. VV, as an employee of Erasmus MC, has conducted research for AstraZeneca. MiS is head of a unit that conducts some research for pharmaceutical companies Pfizer, Novartis, Lilly, and Altana (the SOS Project was not funded or cofunded by any of these companies). All other authors have no conflicts of interest to declare.

  • Ethical approval: Ethical approval was not required for this study.

  • Data sharing: No additional data available.

  • The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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