Healing of Nonsteroidal Anti-inflammatory Drug-Associated Ulcers and Erosions, and Relief of Dyspeptic Symptoms: A Commentary on the New Data

Abstract

Anumber of treatments are available for promoting the healing of gastric and duodenal ulcers associated with the ingestion of nonsteroidal anti-inflammatory drugs). These include the proton pump inhibitors and H2-receptor antagonists, which inhibit gastric acid secretion, and prostaglandin analogs, which suppress gastric acid and are also cytoprotective. A key issue, however, is what represents optimal therapy in peptic ulcer patients who must continue NSAID treatment. To date, the H2-receptor antagonists have been the most extensively studied therapeutic class in this disease area, but the data are conflicting. In a multicenter study by Lancaster-Smith et al, healing of NSAID-associated ulcers with ranitidine, 150 mg twice daily, was significantly lower in patients who continued their NSAID therapy when compared with those who stopped. At 8 weeks, gastric ulcers had healed in 63% of patients who continued NSAID therapy, compared with 95% who stopped. In duodenal ulcer, the 8-week healing rates were 84% in patients who continued NSAID therapy and 100% in those who stopped. In contrast, however, other studies have not shown such an effect of continued NSAID ingestion on ranitidine therapy. In a group of 67 patients, Manniche et al reported similar healing rates with either ranitidine, 150 mg twice daily, or sucralfate, 1 g four times daily, irrespective of whether NSAID therapy was discontinued. Similarly, in a separate study of 149 arthritic patients, the 4-week healing rates with ranitidine, 150 mg twice daily, in patients who continued or discontinued NSAID therapy were 67% and 68%, respectively, for gastric ulcer and 61% and 81%, respectively, for duodenal ulcer. In the same study, the 4-week healing rates in patients treated with placebo who discontinued NSAID therapy were 47% and 42% for gastric and duodenal ulcer, respectively. While prophylaxis of NSAID-associated gastroduodenal ulcers with the prostaglandin analog misoprostol is well documented, data are very limited on its acute use for healing, particularly in patients who continue to take NSAID therapy. Misoprostol, 200 mg four times daily, has been compared with placebo in a double-blind trial involving 77 patients with endoscopically verified gastric ulcer. In this study, the healing rate at 8 weeks was 90% with placebo. Thus, the cumulative healing rate with misoprostol was not better than with placebo at 8 weeks, although it was significantly higher at 4 weeks, possibly suggesting that misoprostol accelerates the healing of gastric ulcers. NSAID therapy was discontinued during this study, however. The efficacy of the proton pump inhibitor omeprazole is well established in the acute management of peptic ulcer disease, but there are only limited data for NSAIDassociated gastroduodenal ulcers. In a double-blind study by Walan et al, omeprazole, 20 mg once daily, was found to be superior to ranitidine, 150 mg twice daily, in healing gastric ulcers, including a subgroup of patients taking concomitant NSAID therapy. The overall healing rate with omeprazole was 69% after 4 weeks, and similarly, was 61% in the subgroup of patients who received concomitant NSAID therapy. In comparison, the overall 4-week healing rate with ranitidine was 59%, but only 32% in patients who were taking NSAIDs. This study suggested that gastric ulcer healing with ranitidine, but not omeprazole, was affected by concomitant NSAID ingestion; however, there were only 68 patients in the subgroup taking NSAIDs. Furthermore, Lauritsen et al have reported, in a double-blind study, that the healing of duodenal ulcers in NSAID users is similar with omeprazole, 20 and 40 mg once daily. In summary, there has been a lack of comparative studies of any size between potentially active drugs, particularly involving patients who need to continue NSAID therapy. The two new, large, randomized, double-blind, multicenter, controlled studies—Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment (ASTRONAUT) and Omeprazole versus Misoprostol of NSAID-Induced Ulcer Management (OMNIUM)—involved almost 1,500 patients who continued to take daily NSAID therapy. They have provided new comparative data on the efficacy and tolerability of original magnification, 20 and 40 mg once daily, ranitidine, 150 mg twice daily, and misoprostol, 200 mg four times daiFrom the Department of Medicine, University of Sydney, The Nepean Hospital, Penrith, New South Wales, Australia. Requests for reprints should be addressed to Nicholas J. Talley, MD, PhD, Division of Medicine, The Nepean Hospital, P.O. Box 63, Penrith, New South Wales 2751, Australia.