Risk of acute myocardial infarction with real-world NSAIDs depends on dose and timing of exposure

PurposeReal-life use of nonsteroidal anti-inflammatory drugs (NSAIDs) is dynamic. This study aimed to characterize the temporal association between time-varying NSAID exposure and acute myocardial infarction (MI). MethodsNested case-control analyses were conducted on a Quebec administrative health cohort. NSAID dose, confounders, and outcome status were determined for each day of follow-up. To better account for dose and timing of past exposures, flexible weighted cumulative exposure models were also fitted. ResultsThe cohort consisted of 233 816 older adults including 21 256 acute MI cases. Dose-related increased risks of MI were found with current use of all NSAIDs. In models not accounting for duration of use, ORs (95%CI) for the most common current daily dose vs. no current exposure were: celecoxib 200mg: 1.16 (1.10, 1.22), diclofenac 150mg: 1.59 (1.38, 1.84), ibuprofen 1200mg: 1.42 (1.17, 1.74), naproxen 750mg: 1.38 (1.21, 1.58), and rofecoxib 25mg: 1.54 (1.43, 1.66). Weighted cumulative exposure models confirmed that all NSAIDsincluding naproxenare associated with an increased risk of MI and suggested that doses taken up to 3weeks ago for rofecoxib, ibuprofen, and naproxen and up to 75days ago for diclofenac and celecoxib may contribute to the current MI risk. However, the celecoxib risk seems to require continuous use for more than 30days, whereas for other NSAIDs, a heightened MI risk occurs within 7days. ConclusionsWeighted cumulative exposure analysis uncovered NSAID-specific differences in the immediate MI risk and how this risk seems to accumulate.