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Therapeutics

Review: 7-day proton-pump inhibitor-based triple therapy is as effective as > 7 days of the same regimen for healing H. pylori–associated peptic ulcer

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ACP J Club. 2005 Sep-Oct;143:49. doi:10.7326/ACPJC-2005-143-2-049


Clinical Impact Ratings

GIM/FP/GP: 6 stars

Hospitalists: 6 stars

Gastroenterology: 5 stars


Source Citation

Gisbert JP, Pajares JM. Systematic review and meta-analysis: is 1-week proton pump inhibitor-based triple therapy sufficient to heal peptic ulcer? Aliment Pharmacol Ther. 2005;21:795-804. [PubMed ID: 15801914]


Abstract

Question

In patients with Helicobacter pylori infection and peptic ulcer, is a 7-day proton-pump inhibitor (PPI)–based triple therapy regimen as effective as > 7 days of the same regimen for healing the peptic ulcer?

Methods

Data sources: MEDLINE, EMBASE/Excerpta Medica, and CINAHL (to August 2004); the Cochrane Library (Issue 3, 2004); and reference lists of selected articles.

Study selection and assessment: Randomized controlled trials (RCTs) in any language except Japanese that endoscopically documented the presence of the ulcer and compared a 7-day combination of a PPI plus 2 antibiotics with the same regimen and PPI prolonged for > 7 days to cure H. pylori and to heal peptic ulcer disease (duodenal [DU] or gastric ulcer [GU]). Trials of patients taking nonsteroidal antiinflammatory drugs (NSAIDs) were excluded. Study quality was assessed for randomization, blinding, and follow-up using the 5-point Jadad scale.

Outcomes: Ulcer healing.

Main results

Of 24 RCTs (n = 2342) that assessed ulcer healing with 7-day PPI-based eradication therapy, 6 RCTs (n = 862) met the selection criteria for comparison of healing with or without subsequent acid-suppression therapy. 5 RCTs (83%) had a Jadad score ≥ 4 out of 5. In the 6 RCTs that were pooled, triple therapy included a PPI (omeprazole [20 mg twice daily] or esomeprazole [20 mg, twice daily]) and 2 antibiotics (clarithromycin [250 to 500 mg, twice daily] and amoxicillin [1 g twice daily], metronidazole [400 mg twice daily], or tinidazole [500 mg twice daily]). The duration of the prolonged PPI regimen was 2 to 4 weeks. Both the 7-day PPI regimen and prolonged PPI regimen groups had high mean ulcer healing rates (91% vs 92%, respectively). Meta-analysis of 6 RCTs using the random-effects model showed that the groups did not differ for ulcer healing (Table).

Conclusion

In patients with Helicobacter pylori infection and peptic ulcer, a 7-day proton pump inhibitor (PPI)–based triple therapy is as effective as the same regimen with PPI prolonged for > 7 days for healing peptic ulcer.

Source of funding: Instituto de Salud Carlos III.

For correspondence: Dr. J.P. Gisbert, University Hospital of La Princesa, Madrid, Spain. E-mail gisbert@meditex.es.


Table. A 7-day proton pump inhibitor (PPI)–based triple therapy (7-d PPI) vs the same regimen with the PPI prolonged for > 7 days (> 7-d PPI) for healing ulcer in Helicobacter pylori at 4 to 9 weeks*

Number of trials (n) Weighted event rates RRR (95% CI) NNT
7-d PPI > 7-d PPI
6 (862) 90% 90% 1% (−3 to 5) Not significant

*Abbreviations defined in Glossary; weighted event rates, RRR, and NNT calculated from data in article using a random-effects model.


Commentary

Treatment of H. pylori–positive DU and GU has revolutionized treatment of peptic ulcer disease. The meta-analysis by Gisbert and Pajares has addressed the question of whether a 7-day PPI-based triple therapy aimed at curing H. pylori is as effective in ulcer healing as the same regimen with the addition of prolonged PPI therapy (> 7 d) in patients with H. pylori–positive DU or GU.

The review showed that the ulcer healing rate in 1289 patients was 86% for all patients combined and 95% for those in whom H. pylori was cured. In 6 trials (n = 862), healing rates were 91% for 7-day anti–H. pylori therapy and 92% after anti–H. pylori treatment plus 2 to 4 more weeks of ongoing treatment with PPI alone. Applying evidence-based medicine criteria, one would have to say that additional acid-suppressive therapy beyond the 7- to 14-day anti–H. pylori therapy is not necessary.

It is doubtful, however, that clinicians will follow this approach in non-DU patients for several reasons. First, the results only apply to uncomplicated (i.e., nonbleeding) or non-NSAID (including aspirin) DUs. NSAID use is common in patients with ulcers. Although some studies included NSAID users, no data for this subgroup were provided. Second, after 1 week, it is generally not known whether H. pylori has been cured, and ulcer healing rates were lower in patients in whom H. pylori persisted (weighted average 86% for eradicated and noneradicated H. pylori vs 95% of patients who were cured). This means that the ulcer was not healed in 1 out of every 7 patients in whom H. pylori persisted. Third, the overall H. pylori cure rate was not mentioned. In clinical practice and certainly in North America, the cure rate is probably lower than the 80% target recommended by most guidelines. Fourth, because the study did not evaluate symptoms, it is not known whether symptoms could be used as a surrogate indicator for unhealed ulcers. Fifth, only 1 trial (n = 73) included GU patients; as discussed by the authors, it is well-known that GUs tend to heal more slowly. Finally, ulcer size is probably important (as discussed by the authors). For large ulcers (e.g., > 1 cm), clinicians should prolong acid suppression to ensure healing.

For small, low-risk DUs, the evidence suggests that 4-week ulcer healing rates will be high, irrespective of success or failure of anti–H. pylori treatment. In practice, failure of anti–H. pylori therapy will probably occur in > 20% of patients. Therefore, for high-risk DUs and most GUs, clinicians may want to continue acid suppression beyond 1 week to increase the probability that the ulcer will be healed, given that H. pylori eradication cannot be assumed or confirmed by the end of 1 week of therapy.

Sander Veldhuyzen van Zanten, MD
Queen Elizabeth II Health Sciences Centre/Dalhousie University
Halifax, Nova Scotia, Canada