Background/Purpose: Certain non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with an increased risk of myocardial infarction (MI). MI risk for different NSAIDs varies largely because of different levels of cyclo-oxygenase (COX) 2 inhibition. Given this differential MI risk, it is clinically important to understand which NSAID options are safer vs. which ones confer an increased risk. For example, naproxen has shown no increased risk of MI, whereas diclofenac has shown an increased risk. However, Meloxicam, which is considered to inhibit COX-2 selectively over COX-1, is used widely across the world, but the risk of MI with Meloxicam has not been quantified.

Methods: The Health Improvement Network (THIN) is a national population-based cohort of over 10 million patients from 580 general practices in the UK. We conducted a nested case-control study of patients between 35 and 89 years of age who had at least 1 year of enrollment between 2000 and 2013 in the cohort and at least 1 prescription for an NSAID. Individuals with a history of MI were excluded. Cases of MI were identified by Read codes and the date of MI was considered the index date. Each case was matched with up to 4 unique controls on age, sex and practice ID. NSAID exposure was categorized as remote (greater than 60 days prior), recent (between 1 and 60 days) or current to the index date. Current NSAID users were further classified as Naproxen, Diclofenac, Meloxicam or other NSAID users. Multivariate logistic regression analysis with 6 categorical variables for NSAID exposure categories was conducted to determine the risk of MI among various current NSAID users compared with that of remote users, adjusting for potential confounders including traditional cardiac risk factors, comorbidities and cardiovascular drug use.

Results: We identified 9817 MI cases and 12860 matched controls from the cohort. The cases had a higher prevalence of traditional cardiac risk factors, more frequent use of cardiovascular medications, and a higher prevalence of chronic kidney disease and inflammatory arthritis (Table 1). The adjusted odds ratio (aOR) for MI with current Meloxicam use was 1.40 (95% CI, 1.15-1.71) as compared with remote NSAID use. While, the aOR with current Naproxen use was 1.01 (95% CI, 0.84-1.22) and with current Diclofenac use was 1.35 (95% CI, 1.21-1.5).

Conclusion: In this large population-based cohort, Meloxicam significantly increased the risk of MI at a level similar to that of Diclofenac. As previously shown, Naproxen was not associated with an increased risk of MI. Drugs like Diclofenac and Meloxicam are widely used across the world should be used cautiously because of the increased risk of MI they pose.