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Meta-analysis: Sequential Therapy Appears Superior to Standard Therapy for Helicobacter pylori Infection in Patients Naive to Treatment

Nadim S. Jafri, MD, MSc; Carlton A. Hornung, PhD, MPH; and Colin W. Howden, MD
[+] Article, Author, and Disclosure Information

Potential Financial Conflicts of Interest:Consultancies: C.W. Howden (Meretek, TAP, Takeda, Santarus, Novartis); Honoraria: C.W. Howden (AstraZeneca, Meretek, Santarus); Grants received: C.W. Howden (AstraZeneca).

Requests for Single Reprints: Colin W. Howden, MD, Division of Gastroenterology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1400, Chicago, IL 60611; e-mail, mailto:c-howden@northwestern.edu.

Current Author Addresses: Dr. Jafri: University of Louisville, 550 South Jackson Street, ACB 3rd Floor, Louisville, KY 40202.

Dr. Hornung: University of Louisville School of Public Heath and Information Sciences, 4063 K Building, 555 South Floyd Street, Louisville, KY 40202.

Dr. Howden: Division of Gastroenterology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1400, Chicago, IL 60611.

From University of Louisville, Louisville, Kentucky, and Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Ann Intern Med. 2008;148(12):923-931. doi:10.7326/0003-4819-148-12-200806170-00226
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Background: Standard proton-pump inhibitor–based therapy for Helicobacter pylori infection fails in up to one quarter of patients. Sequential therapy may be more efficacious.

Purpose: To compare sequential therapy with standard triple therapy for H. pylori infection.

Data Sources: MEDLINE, EMBASE (1981 to October 2007), the Cochrane Central Register of Controlled Trials, and Google Scholar. PubMed and Ovid were the search engines used.

Study Selection: Randomized, controlled trials (RCTs) comparing sequential and standard triple therapies in treatment-naive patients with documented H. pylori infection.

Data Extraction: 3 reviewers independently assessed trial eligibility and quality and extracted data on eradication.

Data Synthesis: The crude rates of H. pylori eradication in 10 RCTs involving 2747 patients were 93.4% (95% CI, 91.3% to 95.5%) for sequential therapy (n = 1363) and 76.9% (CI, 71.0% to 82.8%) for standard triple therapy (n = 1384) (relative risk reduction, 71% [CI, 64% to 77%]; absolute risk reduction, 16 percentage points [CI, 14 to 19 percentage points]). The median rates of adherence were 97.4% (range, 90.0% to 98.9%) for sequential therapy and 96.8% (range, 93.0% to 100%) for standard therapy. Sequential therapy appeared superior in prespecified sensitivity (subgroup) analyses stratified by trial quality; smoking status; diagnosis (ulcer disease or nonulcer dyspepsia); resistance to clarithromycin, imidazoles, or both; duration of triple therapy; and method of diagnosis. Both treatments had similar side effect profiles.

Limitations: Only 1 study was double-blinded. Most patients were from Italy. There was clear evidence of publication bias.

Conclusion: Sequential therapy appears superior to standard triple therapy for eradication of H. pylori infection. If RCTs in other countries confirm these findings, 10-day sequential therapy could become a standard treatment for H. pylori infection in treatment-naive patients.


Grahic Jump Location
Figure 1.
Identification of eligible randomized, controlled trials (RCTs).
Grahic Jump Location
Grahic Jump Location
Figure 2.
Funnel plot of all included studies.

The vertical axis represents the line of no effect, and the horizontal axis represents the log risk ratio. The diagonal lines represent the 95% CI. The circles represent individual studies in the fixed-effects model. The diamond represents the pooled risk ratio and its 95% CI.

Grahic Jump Location




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