open access publication

Article, 2023

Impact of Lifestyle and Socioeconomic Position on the Association Between Non-steroidal Anti-inflammatory Drug Use and Major Adverse Cardiovascular Events: A Case-Crossover Study

In: Drug Safety, ISSN 0114-5916, 1179-1942, Volume 46, 6, Pages 533-543, 10.1007/s40264-023-01298-0

Contributors (8)

Bonnesen, Kasper (0000-0002-8626-2372) (Corresponding author) [1] [2] Pedersen, Lars Henning (0000-0001-6726-1991) [1] [2] Ehrenstein, Vera (0000-0002-3415-3254) [1] [2] Grønkjær, Marie Stjerne (0000-0002-7049-0952) [3] Sørensen, Henrik T Toft (0000-0003-4299-7040) [1] [2] Hallas, Jesper (0000-0002-8097-8708) [4] Lash, Timothy Lee [5] Schmidt, Morten (0000-0002-4935-4059) [1] [2]


  1. [1] Aarhus University
  2. [NORA names: AU Aarhus University; University; Denmark; Europe, EU; Nordic; OECD]
  3. [2] Aarhus University Hospital
  4. [NORA names: Central Denmark Region; Hospital; Denmark; Europe, EU; Nordic; OECD]
  5. [3] Center for Clinical Research and Prevention
  6. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD]
  7. [4] University of Southern Denmark
  8. [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD]
  9. [5] Emory University
  10. [NORA names: United States; America, North; OECD]


IntroductionIt is unknown whether the cardiovascular risks associated with non-steroidal anti-inflammatory drug (NSAID) use differ according to lifestyle and socioeconomic position.ObjectiveWe examined the association between NSAID use and major adverse cardiovascular events (MACE) within subgroups defined by lifestyle and socioeconomic position.MethodsWe conducted a case-crossover study of all adult first-time respondents to the Danish National Health Surveys of 2010, 2013, or 2017, without previous cardiovascular disease, who experienced a MACE from survey completion through 2020. We used a Mantel-Haenszel method to obtain odds ratios (ORs) of the association between NSAID use (ibuprofen, naproxen, or diclofenac) and MACE (myocardial infarction, ischemic stroke, heart failure, or all-cause death). We identified NSAID use and MACE via nationwide Danish health registries. We stratified the analyses by body mass index, smoking status, alcohol consumption, physical activity level, marital status, education, income, and employment.ResultsCompared with non-use, the OR of MACE was 1.34 (95% confidence interval: 1.23–1.46) for ibuprofen, 1.48 (1.04–2.43) for naproxen, and 2.18 (1.72–2.78) for diclofenac. When comparing NSAID use with non-use or the individual NSAIDs with each other, we observed no notable heterogeneity in the ORs within subgroups of lifestyle and socioeconomic position for any NSAID. Compared with ibuprofen, diclofenac was associated with increased risk of MACE in several subgroups with high cardiovascular risk, e.g., individuals with overweight (OR 1.52, 1.01–2.39) and smokers (OR 1.54, 0.96–2.46).ConclusionsThe relative increase in cardiovascular risk associated with NSAID use was not modified by lifestyle or socioeconomic position.


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