NSAIDs may be grouped according to their preference for COX-1 and COX-2 enzymes. Those that favor COX-1 are more likely to cause gastrointestinal side effects. Those that favor COX-2 have a higher risk of cardiovascular effects but less gastrointestinal effects. Higher dosages of NSAIDs tend to result in more COX-2 enzyme inhibition (and more cardiovascular side effects), even in those NSAIDs traditionally seen as low risk (such as ibuprofen). NSAIDs with higher activity against COX-2 enzymes should be used with caution in people with cardiovascular disease or at increased risk of cardiovascular disease.
The safety of non-selective non-steroidal anti-inflammatory drugs (non-selective NSAIDs) has been evaluated by the Medicines Adverse Reactions Committee (MARC). Non-selective NSAIDs do not differentiate between COX-1 and COX-2 in their inhibitory action, and are a separate class of drug to the COX-2 inhibitors. As part of their evaluation, the MARC reviewed adverse reaction reports received by the Centre for Adverse Reactions Monitoring (CARM) and the WHO (Vigibase), together with recently published literature and international regulatory activity.