Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment

Ann Intern Med. 2008 Jun 17;148(12):923-31. doi: 10.7326/0003-4819-148-12-200806170-00226. Epub 2008 May 19.


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.

Publication types

  • Meta-Analysis

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Humans
  • Proton Pump Inhibitors*
  • Sensitivity and Specificity
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Proton Pump Inhibitors