(P-242) Nsaids and Risk of Myocardial Infarction in Patients with No Major Risk Factors: A Nested Case-control Study in the UK Clinical Practice Research Datalink

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used analgesics, and their cardiovascular risk profile is of major public health importance. However, studies of the risk of myocardial infarction (MI) in association with NSAID use have yielded mixed results.

Objectives: The aim of this study was to evaluate the association between traditional and other NSAID use and risk of MI in patients with no major cardiovascular risk factors using data from the Clinical Practice Research Datalink (CPRD) GOLD. This study updates previous results with an additional 15 years of CPRD GOLD data.

Methods: We conducted a nested case-control study in patients aged 40-79 years with a first NSAID prescription between 2006 and 2019. From this population we identified 8,639 MI cases and 34,556 controls with no major risk factors matched on sex, age, general practice, and calendar time. NSAIDs included diclofenac, ibuprofen, naproxen, COX-1 and COX-2 inhibitors and nonselective NSAIDs. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for MI comparing current, recent and past use to non-exposed. Results were categorized according to type and number of NSAID prescriptions prescribed. We also stratified analyses according to use of proton-pump inhibitors (PPIs).

Results: Current diclofenac use was associated with an increased risk of MI that was highest in new users of 1-5 prescriptions (aOR 2.37; 95% CI 1.80 – 3.13) but remained elevated by around twofold in those with longer duration of use. In current ibuprofen users the risk was concentrated in those prescribed 1-5 prescriptions (aOR 2.17; 95% CI 1.57 – 2.99) and declined in those with >5 prescriptions. There was no increased risk in current naproxen users. Adjusted ORs were close to 1.5 for recent and past use of each NSAID. We observed substantially increased risks ranging from 2 to 5 among current and recent diclofenac and ibuprofen users also exposed to PPIs. In those not exposed to PPIs, there was no spike in risk in new current diclofenac users, but ORs rose progressively with increasing number of prescriptions. ORs were only marginally increased among ibuprofen users not exposed to PPIs.

Conclusions: In this study the risk of MI was elevated in current diclofenac users, particularly in those who were also new users of a PPI. The risk was also increased in new users of ibuprofen and PPIs but declined with extended use and was lower in patients not exposed to PPIs. This suggests that observed associations may be explained by protopathic bias, as NSAIDs and PPIs are often prescribed concomitantly for early symptoms of MI.