Cardiovascular risks of continuing vs. initiating NSAIDs after first-time myocardial infarction or heart failure: a nationwide cohort study

Eur Heart J Cardiovasc Pharmacother. 2023 Sep 20;9(6):562-569. doi: 10.1093/ehjcvp/pvad047.

Abstract

Aims: It is unknown whether the cardiovascular risks associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) shortly after first-time myocardial infarction (MI) or heart failure (HF) differ between patients continuing and initiating use.

Methods and results: Using nationwide health registries, we conducted a cohort study of all patients with first-time MI or HF during 1996-2018 (n = 273 682). NSAID users (n = 97 966) were categorized as continuing (17%) and initiating (83%) users according to prescription fillings < 60 days before index diagnosis. The primary outcome was a composite of new MI, HF admission, and all-cause death. Follow-up started 30 days after the index discharge date. We used Cox regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing NSAID users vs. non-users. The most commonly filled NSAIDs were ibuprofen (50%), diclofenac (20%), etodolac (8.5%), and naproxen (4.3%). The composite outcome HR of 1.25 (CI: 1.23-1.27) was driven by initiators (HR = 1.39, 1.36-1.41) and not continuing users (HR = 1.03, 1.00-1.07). The lack of association among continuing users was also observed for individual NSAIDs (ibuprofen and naproxen), except diclofenac (HR = 1.11, 95% CI: 1.05-1.18). Among initiators, the HR was 1.63 (CI: 1.57-1.69) for diclofenac, 1.31 (CI: 1.27-1.35) for ibuprofen, and 1.19 (CI: 1.08-1.31) for naproxen. The results were consistent for both MI and HF patients, the individual components of the composite outcome, and various sensitivity analyses.

Conclusion: NSAID initiators were more susceptible to adverse cardiovascular outcomes after first-time MI or HF than continuing users.

Keywords: Cardiovascular diseases; Epidemiology; NSAIDs; Trends.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Cardiovascular Diseases* / chemically induced
  • Cohort Studies
  • Diclofenac / adverse effects
  • Heart Disease Risk Factors
  • Heart Failure* / diagnosis
  • Heart Failure* / epidemiology
  • Humans
  • Ibuprofen / adverse effects
  • Myocardial Infarction* / diagnosis
  • Myocardial Infarction* / epidemiology
  • Naproxen / adverse effects
  • Risk Factors

Substances

  • Diclofenac
  • Ibuprofen
  • Naproxen
  • Anti-Inflammatory Agents, Non-Steroidal