Abstract
BackgroundUse of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used.ObjectivesTo estimate the risk of AMI for individual NSAIDs.MethodsA nested case-control study was performed from a cohort of new NSAID users ≥18 years (1999–2011) matching cases to a maximum of 100 controls on database, sex, age, and calendar time. Data were retrieved from six healthcare databases. Adjusted odds ratios (ORs) of current use of individual NSAIDs compared to past use were estimated per database. Pooling was done by two-stage pooling using a random effects model (ORmeta) and by one-stage pooling (ORpool).ResultsAmong 8.5 million new NSAID users, 79,553 AMI cases were identified. The risk was elevated for current use of ketorolac (ORmeta 2.06;95%CI 1.83–2.32, ORpool 1.80; 1.49–2.18) followed, in descending order of point estimate, by indometacin, etoricoxib, rofecoxib, diclofenac, fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen (ORmeta 1.12; 1.03–1.22, ORpool 1.00;0.86–1.16). Higher doses showed higher risk estimates than lower doses.ConclusionsThe relative risk estimates of AMI differed slightly between 28 individual NSAIDs. The relative risk was highest for ketorolac and was correlated with COX-2 potency, but not restricted to coxibs.
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce inflammation and provide pain relief
The relative risk was highest for ketorolac and was correlated with COX-2 potency, but not restricted to coxibs
As inhibition of the COX-1 enzyme decreases prostaglandins production, gastrointestinal adverse events including ulcerations and bleeding occur often during non-steroidal anti-inflammatory drugs (NSAIDs) use. This led to development of selective COX-2 inhibitors which after successful market introduction [1,2] were considered with cardiovascular safety resulting in the voluntary withdrawal of rofecoxib in 2004.[3]. The underlying mechanism of increased cardiovascular events may be related to a dysbalance in COX-1 and COX-2 inhibition properties favoring thrombosis by vasoconstriction and platelet aggregation.[4,5]
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce inflammation and provide pain relief They act via reversible, competitive inhibition of cyclo-oxygenase (COX) enzymes. As inhibition of the COX-1 enzyme decreases prostaglandins production, gastrointestinal adverse events including ulcerations and bleeding occur often during NSAID use. This led to development of selective COX-2 inhibitors (coxibs) which after successful market introduction [1,2] were considered with cardiovascular safety resulting in the voluntary withdrawal of rofecoxib in 2004.[3] The underlying mechanism of increased cardiovascular events may be related to a dysbalance in COX-1 and COX-2 inhibition properties favoring thrombosis by vasoconstriction and platelet aggregation.[4,5]. The risk of AMI has only been studied for very few NSAIDs that are frequently used
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