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Clinical question
What is the most effective treatment for patients with Helicobacter pylori
negative dyspepsia?
Bottom line
Omeprazole (and to a lesser extent, ranitidine) are somewhat effective for
patients with Helicobacter pylori (HP) negative dyspepsia, even if patients
with a primary complaint of heartburn or reflux are excluded. The benefit
did not persist through the next 5 months when patients could use
medications as needed rather than in a scheduled manner. Ranitidine was more
cost-effective than omeprazole. It still makes sense to try ranitidine first
for these patients, then stepping up to omeprazole if their symptoms are not
improved adequately, particularly since this is a benign, self-limited
condition.
Reference
Veldhuyzen van Zanten SJ, Chiba N, Armstrong D, et al. A randomized trial
comparing omeprazole, ranitidine, cisapride, or placebo in Helicobacter
pylori negative, primary care patients with dyspepsia: The CADET-HN study.
Am J Gastroenterol 2005; 100:1477-88.
Study design: Randomized controlled trial (double-blinded)
Setting: Outpatient (primary care)
Synopsis
Previous studies have shown that patients with HP positive dyspepsia benefit
from eradication of the infection. This study included patients with
epigastric pain and a variety of other symptoms (bloating, nausea, early
satiety, heartburn, and acid regurgitation) who were HP negative. Patients
were excluded with heartburn as a primary symptom, who had symptoms
consistent with irritable bowel syndrome, or with red flags for complicated
ulcer disease. For the first 2 weeks of the study, the 512 participants
recorded their symptoms without treatment. They were then randomized
(allocation concealed) to receive either omeprazole (Prilosec) 20 mg once
daily, ranitidine (Zantac) 150 mg twice daily, cisapride (Propulsid) 20 mg
twice daily, or placebo. Assignment to the cisapride arm was terminated
early when that drug was found to cause rare cardiac effects. Patients and
outcome assessors were properly blinded and analysis was by intention to
treat. Patients took the study medications as directed for the first 4 weeks
of the study, and after that were able to take them on an as-needed basis
for the final 5 months of the study with an antacid as a rescue medication.
The primary outcome was the Global Overall Severity score, a validated
7-point scale, at 4 weeks. All patients had a score of at least 4 during the
initial 2 weeks, and success was defined as a score of 0 or 1 (no or minimal
symptoms). Approximately 95% of participants in each group completed the
4-week study, and 85% completed the entire 6-month study. Treatment success
at 4 weeks was seen in 51% of those taking omeprazole, 36% taking
ranitidine, 31% taking cisapride, and 23% taking placebo. Omeprazole was
significantly more effective than all the other treatments and placebo
(number needed to treat [NNT] compared with placebo = 3; compared with
ranitidine = 7). Ranitidine was also more effective than placebo (NNT = 5).
The response rate for omeprazole was a bit lower for patients with no or
minimal heartburn or regurgitation (49%), a bit better if they had at least
mild heartburn or regurgitation (54%). If patients with heartburn as the
most bothersome symptom (approximately 1 in 4 patients) were excluded the
response rate dropped to 43% (versus 25% for placebo; P = .009). However,
there was no significant difference in the percentage of responders between
groups at 6 months: 44% for omeprazole, 41% for ranitidine, 40% for
cisapride, and 35% for placebo. A subgroup analysis of responders at 4 weeks
who remained responders at 6 months remained higher for omeprazole than for
ranitidine or placebo (31% vs 21% vs 13.5%; P = .001). Of the active
treatment groups, the mean societal cost per patient in Canadian dollars was
lower for ranitidine ($225) than for omeprazole ($364). The incremental
cost-effectiveness (ie, how much more you have to spend to improve quality
of life) was also lower for ranitidine than for omeprazole. However,
decreases in the price of omeprazole might alter this calculation.
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