Archief Roodbont

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Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with high risk for gastrointestinal bleeding. This risk can be lowered by using a cyclooxygenase-2–selective NSAID (coxib) or by adding a proton-pump inhibitor (PPI) to nonselective NSAID therapy. Recent guidelines recommend that these approaches be used for patients who require NSAIDs but have risk factors for NSAID-associated ulcers. However, neither approach completely eliminates bleeding risk. An alternative strategy is to prescribe cotherapy with a coxib and a PPI, but this approach has not been tested in randomized trials.

To address this issue, investigators recruited 441 consecutive high-risk patients with nonselective-NSAID-associated ulcer bleeding who were admitted to a single hospital in Hong Kong. NSAIDs were stopped, and the patients received PPI therapy and, if necessary, treatment for Helicobacter pylori infection. After endoscopic documentation of ulcer healing and confirmation that H. pylori had been eradicated, 273 patients were enrolled. All patients received a coxib (celecoxib; 200 mg twice daily); half were randomized to receive a PPI (esomeprazole; 20 mg twice daily), and half received twice-daily placebo. Investigators followed patients for a median of 13 months to identify GI bleeding, efficacy of symptom relief, and adherence to study protocol. Bleeding episodes were adjudicated by an independent panel.

After 13 months, 8.9% of the celecoxib-alone group had experienced GI bleeding, compared with none of the combination-therapy group (P=0.0004). Efficacy and adverse events were similar in the two groups. The authors concluded that, in high-risk patients, risk for GI bleeding was lower with a coxib plus a PPI than with a coxib alone.

Comment

These data suggest that patients with previous NSAID-associated ulcer bleeding should receive a PPI, but the investigators did not compare a nonselective NSAID plus a PPI to a coxib plus a PPI, so the benefit of the coxib is difficult to quantify. However, the complete absence of bleeding in the combination-therapy group and the results of previous studies suggest that nonselective NSAIDS are likely to impart a higher risk than do coxibs, with or without concomitant PPI therapy. The effect of PPI therapy in this study is impressive, because patients in both arms were allowed to take low-dose aspirin for cardiovascular prophylaxis (after the cardiovascular risks of coxibs were reported); other studies have shown that the protective effect of coxibs (compared with nonselective NSAIDs) is attenuated by concomitant aspirin therapy (Journal Watch Gastroenterology Mar 30 2007). When deciding on the appropriate strategy for an individual patient, a physician must weigh the potential cardiovascular risks of prescribing a coxib, whether alone or with a PPI, against potential risk for GI bleeding.

# posted by roodbont @ 2:32 PM