NSAIDs and GI Bleeding
Abstract & Commentary
Synopsis: Current guidelines for NSAID use in patients at high risk for ulcer disease recommend use of NSAIDs selective for cyclo-oxygenase-2 inhibition or nonselective NSAIDs plus a proton pump inhibitor. This study compared diclofenac plus omeprazole with celecoxib in patients with previous GI hemorrhage. Neither regimen successfully prevented rebleeding, and both exhibited significant toxicities.
Source: Francis KL, et al. N Engl J Med. 2002;347(26): 2104-2110.
This Hong Kong study addressed a topic of great clinical relevance: the avoidance of ulcer re-activation and bleeding in patients requiring nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis treatment. In this trial, 287 patients were studied over 6 months: 144 receiving celecoxib 200 mg twice daily and 143 receiving diclofenac 75 mg twice daily plus 20 mg of omeprazole. Previous studies have suggested that COX-2 selective NSAID use leads to reduced GI events, and American College of Rheumatology guidelines strongly recommend the use of this drug class in patients at risk for ulcer disease. Along with high-dose H2-receptor antagonists and misoprostol, proton pump inhibitors (PPIs) have also been shown to lessen GI complications.
This is the first trial to directly compare these 2 approaches in patients with prior documented ulcer hemorrhage. All patients studied were Helicobacter pylori-negative, and all had previous endoscopically documented gastric or duodenal ulcer healing. The primary study end point was endoscopically documented ulcer bleeding (following presentation with hematemesis and/or melena). Anti-arthritic efficacy did not differ between the 2 regimens. Seven patients bled with celecoxib therapy, and 9 bled who received omeprazole and diclofenac. Renal adverse events were common including hypertension, peripheral edema, and renal failure (24.3% with celecoxib and 30.8% with diclofenac and omeprazole). These toxicities were especially prominent in patients with baseline renal impairment.
Comment by Malcolm Robinson, MD, FACP, FACG
This study substantiates the intuitive notion that ulcer complications are far better markers of NSAID injury than the surrogate end points so often used in endoscopic studies of normal subjects or patients. In an editorial in the issue of the New England Journal of Medicine, Dr. David Graham complained that this study combined patients who had H pylori eradicated with those who had never been infected despite the absence of data that these groups would be comparable.1 Nevertheless, both he and I would agree that this is the best study yet to elucidate data regarding NSAIDs and ulcer complications.
It is discouraging that neither PPI prophylaxis nor use of COX-2 NSAID therapy can avert ulcer recurrence and bleeding in this setting. The next generation of studies should probably combine COX-2 NSAID therapy with antisecretory drugs and/or misoprostol. An alternative might be more aggressive PPI therapy (eg, a second-generation PPI and/or b.i.d. therapy and possibly with addition of low-dose H2RA therapy at bedtime). Dr. Graham believes that all H pylori should be eliminated in patients requiring long-term NSAID therapy, but I personally still do not find the data fully supportive of this approach.
Dr. Robinson is Medical Director of Oklahoma Foundation for Digestive Research and Clinical Professor of Medicine at University of Oklahoma College of Medicine in Oklahoma City, OK.
Reference
1. Graham D. N Engl J Med. 2002;347(26):2162-2164.
Current guidelines for NSAID use in patients at high risk for ulcer disease recommend use of NSAIDs selective for cyclo-oxygenase-2 inhibition or nonselective NSAIDs plus a proton pump inhibitor. This study compared diclofenac plus omeprazole with celecoxib in patients with previous GI hemorrhage. Neither regimen successfully prevented rebleeding, and both exhibited significant toxicities.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content