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Risk of cardiovascular disease with high-dose versus low-dose use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis
  1. Ji-Won Kim1,
  2. Jun Sik Yoon2,
  3. Sojeong Park3,
  4. Hasung Kim3,
  5. Ji Sung Lee4,
  6. Jung-Yoon Choe1
  1. 1Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea (the Republic of)
  2. 2Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea (the Republic of)
  3. 3Data Science Team, Hanmi Pharm Co Ltd, Seoul, Korea (the Republic of)
  4. 4Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (the Republic of)
  1. Correspondence to Dr Ji-Won Kim, Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, 42472, Korea (the Republic of); kimjw689{at}cu.ac.kr

Abstract

Objective To investigate the risk of cardiovascular disease (CVD) associated with increasing dose of a non-steroidal anti-inflammatory drug (NSAID) in patients with ankylosing spondylitis (AS).

Methods Using the Korean National Health Insurance database, patients newly diagnosed with AS without prior CVD between 2010 and 2018 were included in this nationwide cohort study. The primary outcome was CVD, a composite outcome of ischaemic heart disease, stroke or congestive heart failure. Exposure to NSAIDs was evaluated using a time-varying approach. The dose of NSAIDs was considered in each exposure period. Cox proportional hazard regression was used to investigate the risk of CVD associated with NSAID use.

Results Of the 19 775 patients (mean age, 36 years; 75% were male), 19 706 received NSAID treatment. During follow-up period of 98 290 person-years, 1663 cases of CVD occurred including 1157 cases of ischaemic heart disease, 301 cases of stroke and 613 cases of congestive heart failure. Increasing dose of NSAIDs was associated with incident CVD after adjusting for confounders (adjusted HR (aHR) 1.10; 95% CI 1.08 to 1.13). Specifically, increasing dose of NSAIDs was associated with incident ischaemic heart disease (aHR 1.08; 95% CI 1.05 to 1.11), stroke (aHR 1.09; 95% CI 1.04 to 1.15) and congestive heart failure (aHR 1.12; 95% CI 1.08 to 1.16). The association between NSAID dose and higher CVD risk was consistent in different subgroups.

Conclusion In a real-world AS cohort, higher dose of NSAID treatment was associated with a higher risk of CVD, including ischaemic heart disease, stroke and congestive heart failure.

  • Cardiovascular Diseases
  • Spondylitis, Ankylosing
  • Anti-Inflammatory Agents, Non-Steroidal

Data availability statement

Data are not available to the public because they are only accessible in an analysis centre with permission from the Korea National Health Insurance Sharing Service.

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Data availability statement

Data are not available to the public because they are only accessible in an analysis centre with permission from the Korea National Health Insurance Sharing Service.

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors Conceptualisation: J-WK. Methodology: J-WK and JSY. Formal analysis: J-WK, JSY, SP, HK and JSL. Funding acquisition: J-WK. Investigation: J-WK. Data curation: J-WK. Supervision: J-WK, JSY, JSL and J-YC. Writing—original draft preparation: J-WK. Writing—review and editing: J-WK, JSY, JSL and J-YC. J-WK is the guarantor who accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish.

  • Funding This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT) (No. 2022R1F1A1073837).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.