Gastrointestinal safety of COX-2 specific inhibitors.
Coxibs are a major advance in the therapy of patients with painful and inflammatory conditions. At present, the theoretical harm that derives from inhibiting vascular COX-2 has not emerged as a significant risk, although more research is needed. What has emerged is that some NSAIDs, particularly naproxen, may have an aspirin-like effect in reducing the risk of vascular disease, although more research is needed. Whether this finding is sufficient to recommend naproxen for the management of patients with arthritis who also require vascular protection is intriguing and worth further evaluation. It is widely believed and maintained that coxibs have the greatest potential value in patients with other risk factors for ulcer disease, and this seems likely to be the case for patients taking corticosteroids or anticoagulants and probably those who are elderly. Dosing should be [figure: see text] cautious in old patients, however, because of the ability of NSAIDs and coxibs to cause fluid retention, heart failure, and hypertension. It is less clear that coxibs reduce risk sufficiently in patients with previous ulceration (particularly recent) to make them a better strategy than acid co-therapy. This possibility requires further evaluation, as does the competing value of the 2 strategies for patients infected with H. pylori. If coxibs are used in patients with H. pylori-associated risks, there are grounds to recommend eradication. For patients taking aspirin or drugs [figure: see text] with an aspirin-like effect, the intrinsic risk of these drugs may mandate use of acid suppression and obviate the use of coxibs (Fig. 8). Available data suggest that the risk reduction in patients with no risk factors who use coxibs may be almost as great as in patients with risk factors, with the added advantage that patients may be taken to a state that is virtually free of any risk of ulcer complications that otherwise might require additional therapy. Contrary to current popular truisms, the greatest value of coxibs may be in patients without risk factors because it is in this unconfounded group that the ability of coxibs to free patients of ulcer risk appears to be delivered in full.
Hawkey
C J
CJ
Division of Gastroenterology, University Hospital, Nottingham, United Kingdom.
Jones
J I
JI
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000367:Age Factors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004357:Drug Synergism; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000627:therapeutic use; D008565:Membrane Proteins; D009288:Naproxen / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000382:microbiology / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases; D013450:Sulfones
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin