Risk of acute myocardial infarction with real‐world <scp>NSAID</scp>s depends on dose and timing of exposure
Bibliographic record
Abstract
PURPOSE: Real-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). METHODS: Nested 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. RESULTS: The 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 200 mg: 1.16 (1.10, 1.22), diclofenac 150 mg: 1.59 (1.38, 1.84), ibuprofen 1200 mg: 1.42 (1.17, 1.74), naproxen 750 mg: 1.38 (1.21, 1.58), and rofecoxib 25 mg: 1.54 (1.43, 1.66). Weighted cumulative exposure models confirmed that all NSAIDs-including naproxen-are associated with an increased risk of MI and suggested that doses taken up to 3 weeks ago for rofecoxib, ibuprofen, and naproxen and up to 75 days ago for diclofenac and celecoxib may contribute to the current MI risk. However, the celecoxib risk seems to require continuous use for more than 30 days, whereas for other NSAIDs, a heightened MI risk occurs within 7 days. CONCLUSIONS: Weighted cumulative exposure analysis uncovered NSAID-specific differences in the immediate MI risk and how this risk seems to accumulate. KEY POINTS Accurate assessment of drug safety requires an etiologically correct model encompassing all relevant aspects of exposure. Weighted cumulative exposure models suggest that the relative importance of past doses on the risk of MI differs among NSAIDs. All common NSAIDs are associated with an increased MI risk. Celecoxib MI risk seems to depend on continuously using the drug for more than 30 days, whereas for ibuprofen, rofecoxib, diclofenac, and naproxen, a heightened MI risk occurs within 7 days of use.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".