Use of Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Relation to Cardiovascular Events. A Systematic Pharmacoepidemiological Review

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used, having numerous indications. However, despite their therapeutic role, they are associated with serious cardiovascular (CV) adverse events. Objectives-Methods: This review comprising recent observational studies and meta-analyses over the past few years aims at updating the assessment of CV adverse events, namely stroke, myocardial infarction (MI), CV death, atrial fibrillation (AF), serious bleeding and heart failure related to the use of 4 of the most widely prescribed NSAIDs: ibuprofen, naproxen, diclofenac and mefenamic acid. Results: The best safety profile related to MI was found for naproxen, while the worst safety profile, with excessively increased risk for stroke, MI and major bleeding, was for diclofenac. Naproxen showed higher risk for major bleeding than ibuprofen and the risk for stroke was slightly higher than ibuprofen. Regarding heart failure, ibuprofen presented the highest risk while the highest risk for AF was attributed to the current use of diclofenac. There are few data related to mefenamic acid, which showed a strong association with increased risk for stroke and a moderately increased risk for MI. Conclusion: Further research is needed in order to devise new guidelines for safer use of NSAIDs.