Diclofenac has a transdermal preparation, and there are parenteral preparations of NSAIDs such as ketorolac. The NSAID compounds are for the most part administered orally. Rofecoxib was found to be associated with increased CV events at doses of 50 mg daily and not at 25 mg daily. Since patients with CAD are on aspirin, this interaction is of public health importance such that the FDA has issued a warning that aspirin and ibuprofen should be given 2 hours apart. Fairly detailed observations from registries and clinical trials have uncovered an interaction between ibuprofen and aspirin. In general the longer the half-life, the greater the CV toxicity. Naproxen and celecoxib are relatively safe in this regard. Most NSAIDs, by their effect on the renal system, raise blood pressure to some degree. In clinical trials, agents that raise systolic blood pressure by 3 mm or greater are associated with greater cardiovascular (CV) events. Rofecoxib (Vioxx) is highly COX-2 selective. The more COX-2 selective an agent, the greater its cardiotoxicity. In their most recent scientific statement, the American Heart Association has put a lot of weight on this variable.
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