title: Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: Systematic review and meta-analysis of efficacy and tolerability.
abstract: OBJECTIVE
  Recent treatment guidelines recommend two first-line therapies for Helicobacter pylori infection: proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole (quadruple therapy) or PPI, clarithromycin, and amoxicillin (triple therapy). We performed a systematic review and meta-analysis to compare the efficacy and tolerability of these regimens as first-line treatment of H. pylori.
  
  
  METHODS
  A search of MEDLINE, EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials, ACP Journal Club, the Database of Abstracts of Reviews of Effectiveness, Cochrane Methodology Register, Health Technology Assessment Database, and abstracts from prominent gastrointestinal scientific meetings was carried out. Randomized controlled trials (RCTs) comparing bismuth quadruple therapy to clarithromycin triple therapy were selected for meta-analysis. Two independent reviewers extracted data, using standardized data forms. Meta-analysis was carried out with the metan command in Stata 10.1. Funnel plots and subgroup analyses were carried out.
  
  
  RESULTS
  Nine RCTs (N=1,679) were included. Although dosing regimens of clarithromycin triple therapy were quite consistent between trials, dosing regimens varied considerably for bismuth quadruple therapy. Bismuth quadruple therapy achieved eradication in 78.3% of patients, whereas clarithromycin triple therapy achieved an eradication rate of 77.0% (risk ratio (RR)=1.002, 95% confidence interval (CI): 0.936-1.073). There was moderate heterogeneity and no evidence for significant publication bias. Subgroup analyses by study location, treatment duration, and study population did not account for the heterogeneity. There were no statistically significant differences in side effects yielded by quadruple vs. clarithromycin triple therapy (RR=1.04, 95% CI: 1.04-1.14).
  
  
  CONCLUSIONS
  Quadruple and triple therapies yielded similar eradication rates as primary therapy for H. pylori infection. Both therapies yielded suboptimal eradication rates. Patient compliance and side effects are similar for quadruple and triple therapies.
authors.affiliation: University of Michigan Medical Center, Ann Arbor, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Luther
authors.forename: Peter D R
authors.initials: PD
authors.lastname: Higgins
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Schoenfeld
authors.forename: Paul
authors.initials: P
authors.lastname: Moayyedi
authors.forename: Nimish
authors.initials: N
authors.lastname: Vakil
authors.forename: William D
authors.initials: WD
authors.lastname: Chey
mesh_terms: D000658:Amoxicillin / Q000627:therapeutic use; D000863:Antacids / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001729:Bismuth / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D008795:Metronidazole / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D010349:Patient Compliance; D017410:Practice Guidelines as Topic; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013752:Tetracycline / Q000627:therapeutic use
chemical_list: D000863:Antacids; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D054328:Proton Pump Inhibitors; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline; D017291:Clarithromycin; D001729:Bismuth