INTRODUCTION — Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, cause considerable morbidity and mortality related to gastric and duodenal ulcer toxicity, particularly by causing gastrointestinal (GI) bleeding. NSAIDs are also important causes of GI bleeding in children [1].
The treatment of gastroduodenal toxicity associated with NSAID therapy will be reviewed here. Modalities used for primary and secondary prevention of gastroduodenal toxicity, including the role of cyclooxygenase (COX)-2 selective NSAIDs, are discussed separately as is the pathogenesis of the gastroduodenal toxicity. (See "NSAIDs (including aspirin): Pathogenesis and risk factors for gastroduodenal toxicity" and "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity" and "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity".)
TREATMENT — If a patient develops an ulcer while on a nonsteroidal antiinflammatory drug (NSAID) or low-dose aspirin, the NSAID or aspirin should be stopped if at all possible and traditional ulcer therapy with a proton pump inhibitor or an H2 antagonist started. Proton pump inhibitors are preferred because they are associated with superior ulcer healing [2-8] (see "Peptic ulcer disease: Treatment and secondary prevention"). If the patient has been taking low-dose aspirin for cardiovascular prophylaxis, there is no consensus as to when to resume the aspirin. The indication for the low-dose aspirin should be reviewed and the severity of the ulcer presentation considered. For most patients, the author recommends low-dose aspirin, if still indicated, be restarted approximately three to five days after initiating therapy with a proton pump inhibitor.
As in all patients with peptic ulcers, the patient's Helicobacter pylori (H. pylori) status should also be assessed (if not done previously) [9]; if positive, appropriate therapy for H. pylori should be instituted [10]. However, the sensitivity of H. pylori testing in the setting of acute GI bleeding is significantly reduced. (See "Treatment regimens for Helicobacter pylori in adults" and "Peptic ulcer disease: Treatment and secondary prevention", section on 'Eradication of Helicobacter pylori (H. pylori)' and "Indications and diagnostic tests for Helicobacter pylori infection in adults", section on 'Patient undergoing upper endoscopy'.)
For patients who must remain on low-dose aspirin, NSAID therapy, or both, randomized trials have shown that ulcer healing occurs more rapidly with a proton pump inhibitor than an H2 antagonist [5,6], misoprostol [7], or sucralfate [8]. Trials comparing proton pump inhibitor with an H2 antagonist were performed with ranitidine, which has since been withdrawn due to unacceptable levels of N-nitrosodimethylamine (NMDA) but had comparable efficacy with other H2 antagonists. (See "Antiulcer medications: Mechanism of action, pharmacology, and side effects", section on 'Adverse effects'.)
●In one trial, 541 patients who had ulcers or numerous (>10) erosions in either the stomach or duodenum and who required continuous treatment with NSAIDs were randomly assigned to treatment with omeprazole (20 or 40 mg PO daily) or ranitidine for four or eight weeks [5]. At eight weeks, healing rates were greater with omeprazole (80 and 79 versus 63 percent with ranitidine).
●In a second trial, 353 patients with benign gastric ulcers who continued to receive stable doses of NSAIDs were randomly assigned to treatment with lansoprazole (15 or 30 mg PO daily) or ranitidine for eight weeks [6]. Healing rates were higher in patients treated with lansoprazole as compared with ranitidine (69 and 73 percent versus 53 percent, respectively).
●In another trial, 935 patients who had ulcers or numerous (>10) erosions in the stomach or duodenum (or both) and who required continuous treatment with NSAIDs were randomly assigned to treatment with omeprazole (20 or 40 mg PO daily) or misoprostol (200 mcg four times per day). Patients were treated for four weeks or, in the absence of ulcer healing, eight weeks [7]. The rates of healing of gastric ulcers (87 versus 73 percent) and duodenal ulcers (93 versus 77 percent) were significantly higher with omeprazole (20 mg) than with misoprostol. The healing rates with 40 mg per day of omeprazole were also superior to misoprostol.
●The efficacy of omeprazole (20 mg daily) was compared to sucralfate (2 g twice daily) in a much smaller study of 98 patients with gastric and duodenal ulcers who required continued treatment with NSAIDs [8]. At eight weeks, omeprazole was significantly superior to sucralfate for healing gastric ulcers (87 versus 52 percent); the differences in the rates of healing of duodenal ulcers (95 versus 73 percent) did not reach statistical significance.
There are no data that suggest that any of the available proton pump inhibitors are more efficacious than another in inducing ulcer healing. The table lists the available medications and their usual dose (table 1).
Duration of PPI therapy and role of endoscopy — Treatment with a PPI is generally continued for four to eight weeks depending on the ulcer location, size, and severity of the initial clinical presentation. In general, we suggest PPI therapy (eg, omeprazole 20 to 40 mg daily or equivalent dose of an alternative PPI) for four to six weeks for ulcers <1 cm (especially for duodenal ulcers) and PPI therapy for six to eight weeks for ulcers ≥1 cm (especially for gastric ulcers). Endoscopic follow-up to assess ulcer healing is usually unnecessary for duodenal ulcers, but should be performed to assess healing of gastric ulcers if there had been any concern that malignancy had not been excluded at the initial endoscopy.
Maintenance PPI therapy is indicated in patients who must remain on or resume low-dose aspirin or NSAID or treatment. (See "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity".) In the author’s opinion, and those of others [11], the proven benefits of PPI maintenance therapy for secondary prevention of NSAID- or low dose aspirin-associated ulcers considerably outweigh potential risks of long term PPI therapy.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: NSAID-related ulcer complications".)
SUMMARY AND RECOMMENDATIONS
●For patients who develop a symptomatic gastric or duodenal ulcer while on a nonsteroidal antiinflammatory drug (NSAID) and/or low-dose aspirin, the NSAID and/or aspirin should be discontinued.
●For patients in whom the NSAID and/or low-dose aspirin can be discontinued, we recommend treating with a proton pump inhibitor for four to eight weeks (Grade 1A). (See 'Treatment' above.)
●For patients in whom the NSAID or low-dose aspirin cannot be stopped or must be restarted before the ulcer is healed, we recommend treatment with a proton pump inhibitor (table 1) (Grade 1A). Maintenance therapy with a PPI is also warranted in such patients. (See "Peptic ulcer disease: Treatment and secondary prevention".)
●The patient's H. pylori status should also be assessed; if positive, appropriate therapy should be instituted. (See "Treatment regimens for Helicobacter pylori in adults" and "Indications and diagnostic tests for Helicobacter pylori infection in adults", section on 'Patient undergoing upper endoscopy'.)
