Between 10% and 15% of older Americans use a prescription nonsteroidal anti-inflammatory drug (NSAID) at least once daily. In addition, it is estimated that the use of over-the-counter nonprescription NSAIDs, which include aspirin, may be five to seven times greater than for prescribed NSAIDs. Numerous studies have confirmed that NSAIDs are clinically effective analgesic agents and that, when given specifically in the form of cardioprotective doses of aspirin (75-325 mg/day), they significantly reduce the risk for cardiovascular events. Although NSAIDs do not differ significantly in terms of their ability to relieve pain, they do differ in their side-effect profiles, which are probably related to their mechanism of action.
NSAIDs may be classified as agents that inhibit both isoforms of cyclooxygenase (COX-1 and COX-2) and as agents that are more selective for COX-2. Until recently, all marketed NSAIDs inhibited COX-1 and COX-2, a property that contributed to the gastrointestinal mucosal injury profile of these agents. This injury profile and its associated complications have been estimated to result in more than 100,000 hospitalizations and more than 16,000 deaths annually. The recent availability of the COX-2 selective agents has demonstrated a reduced risk of gastrointestinal mucosal injury. However, there appears to be a delicate balance between the ability to protect the gastric mucosa and the effect on thrombotic events. Although selective COX-2 inhibitors appear to protect the gastric mucosa as a result of their selectivity, this same mechanism may cause an increased tendency toward thrombosis; several analyses suggest that these agents, compared with traditional NSAIDs, may increase a patient’s risk for cardiovascular events.
Gastrointestinal mucosal injury and complications associated with the use of COX-1/COX-2 NSAIDs, along with the risk of cardiovascular effects associated with selective COX-2 NSAIDs, have left clinicians in a quandary as to the ideal analgesic-cardioprotec-tive regimen to use. This dilemma has been further complicated by recent studies demonstrating that generic naproxen (Naprosyn canadian, Roche) is more cardioprotective than other NSAIDs.
This article reviews the pathophysiology of the inflammatory response and the pharmacological mechanisms of NSAID activity. Criteria that identify patients at risk for gastrointestinal mu-cosal injury or cardiovascular events are also presented. In a separate article in this issue, Drs. Fendrick and Garabedian-Ruffalo present a clinician’s guide to selecting NSAID therapy and, if applicable, antisecretory-gastroprotective therapy, as determined by the patient’s risk for gastrointestinal injury and his or her concurrent use of aspirin.