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

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.