Esomeprazole 40 mg Once a Day in Patients with Functional Dyspepsia
Abstract & Commentary
By Malcolm Robinson MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speaker's bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca, and Centocor.
Synopsis: Functional dyspepsia cannot reliably be diagnosed using symptoms alone. Esomeprazole therapy is not effective vs placebo in an 8-week study of endoscopy-negative patients with histories thought to be diagnostic of FD.
Source: Sander Veldhuyzen van Zanten, et al. Am J Gastroenterol. 2006. Epub ahead of print.
Functional dyspepsia (FD) has been defined as persistent or recurrent upper abdominal pain in the absence of organic disease by upper endoscopy and other appropriate investigations. Pathophysiology probably has many variations, but some patients seem to respond to acid suppression. It has been assumed that many patients with FD relieved by acid inhibition have unrecognized GERD despite the fact that FD is supposed to exclude patients with dominant heartburn or regurgitation. In previous FD studies, esomeprazole treatment (ESO) has resulted in better outcomes than omeprazole, ranitidine, or cisapride. The present study was designed to test efficacy of ESO vs placebo one half hour before breakfast. FD patients were from primary care settings and specifically did not have dominant GERD symptoms.
Forty nine primary care centers in Canada were involved in the trial, and 109 patients were randomized to ESO and 115 received placebo. All patients had normal pre-study endoscopies. Exclusions included IBS, previous history of mucosal acid peptic disease, and maintenance acid suppressive therapy within 6 months of study entry. Urea breath testing for H. pylori was done at baseline, but results were not disclosed to investigators during the study. Data on daily symptoms were gathered. 'Symptom relief' was defined as minimal or no symptoms during the 2 days prior to 4 and 8 week evaluations. Sample size was calculated prior to initiating the trial; 41% of prospective enrollees were disqualified at screening endoscopy with 23.6% having erosive esophagitis, 1.5% gastric ulcer, 4.2% duodenal ulcer, 12.3% gastric erosions, and 5.3% duodenal erosions. Thirty nine patients were eliminated because symptoms at study entry 7-10 days post-endoscopy were no longer moderate or greater in intensity. A wide range of symptoms were present in those accepted for the study: 26.8% bloating, 25% epigastric pain, 10.7% postprandial fullness. Overall prevalence of H. pylori was 22.8%, matched between recipients of ESO and placebo. Symptom relief as defined at 8 weeks did not differ between ESO and placebo although the 4-week data were significantly different (relief in 50.5% on ESO vs 32.2% on placebo; P = 0.009).
Commentary
The study was commissioned and supported by AstraZeneca Canada (marketer of esomeprazole). Obviously disappointed with the results of the study, the authors extensively speculated regarding the possible explanations for the lack of efficacy of ESO vs placebo at the conclusion of this 8-week study. However, at least for this reviewer, the bottom line here is the absence of long-term efficacy of aggressive acid suppression in functional dyspepsia. The study did do a good job of showing that the clinical diagnosis of FD is highly imprecise in that many of the patients with this 'diagnosis' were found on screening endoscopy to have a wide range of pathologies. It has long been clear that acid suppressive therapy is grossly over prescribed, and this study is further evidence that the chronic use of PPIs in functional dyspepsia cannot be scientifically justified.
Functional dyspepsia cannot reliably be diagnosed using symptoms alone. Esomeprazole therapy is not effective vs placebo in an 8-week study of endoscopy-negative patients with histories thought to be diagnostic of FD.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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