An increased risk of cardiovascular thrombotic events in users of NSAIDs was first demonstrated for rofecoxib. This risk seems to be related to the COX-2 inhibitory potency and has been found with most NSAIDs except naproxen. Two main hypotheses have been advanced: an imbalance between COX-1-dependent platelet production of thromboxane and partly COX-2-dependent endothelial production of prostacyclin, and a COX-2-dependent increase in blood pressure.