Peptic ulcer disease is a well-recognised complication of NSAID use. Inhibition of COX-1 in the gastrointestinal tract leads to a reduction of prostaglandin secretion and its cytoprotective effects in gastric mucosa. This therefore increases the susceptibility to mucosal injury.6 Inhibition of COX-2 may also play a role in mucosal injury.
Risk factors
Gastrointestinal toxicity with NSAIDs, including low-dose aspirin, is highest in patients with risk factors. These include increased age (>65 years), past history of peptic ulcer disease, heart disease, and co-prescription of antiplatelets, corticosteroids and anticoagulants. In addition, using higher doses of NSAIDs leads to an increased risk of upper gastrointestinal complications.7 Prolonged NSAID use and H. pylori infection are also associated with an increased risk of gastrointestinal toxicity.
In patients who are chronic users of NSAIDs and who have no risk factors, only 0.4% have serious adverse events. However, the risk is as high as 9% in patients with multiple risk factors.8 Before prescribing for a patient with risk factors always consider if there are alternatives to NSAIDs.
Which NSAID to use?
All NSAIDs cause some degree of gastrointestinal toxicity. Large pooled data from placebo-controlled trials show that all evaluated NSAIDs including COX-2 inhibitors, diclofenac, ibuprofen and naproxen were associated with an increased risk of gastrointestinal injury.9 However, this risk varies between the drugs. The relative risk of upper gastrointestinal complications for aceclofenac, celecoxib and ibuprofen is low (<2). Diclofenac, meloxicam and ketoprofen are intermediate (2–4) while naproxen, indomethacin and diflunisal have a higher relative risk (4–5). The highest pooled relative risk is associated with piroxicam (7.4) and ketorolac (11.5).7
Drugs with greater selectivity for COX-2 than COX-1 should have less gastrointestinal toxicity. Large pooled data showed that the predicted absolute annual risk of upper gastrointestinal complications was lower for COX-2 inhibitors than naproxen and ibuprofen.7 However, COX-2 inhibitors are associated with an increased risk of cardiovascular events. There is little evidence of an increased risk of cardiovascular complications with use of a low dose of diclofenac. However, to avoid possible cardiovascular complications the use of NSAIDs should be at the lowest possible dose and for the shortest time.