title: Tiotropium HandiHaler improves the survival of patients with COPD: a systematic review and meta-analysis.
abstract: BACKGROUND
  Tiotropium HandiHaler (TioH) has been shown to improve lung function, exacerbations, and quality of life when added to the pharmacotherapy of patients with stable chronic obstructive pulmonary disease (COPD). The purpose of this meta-analysis was to synthesize current evidence regarding the impact of TioH on the survival rate of these patients, which is still controversial.
  
  
  METHODS
  A systematic search in the electronic databases of the Cochrane Library, Medline, Scopus, EMBASE, PschINFO, CINAHL, and Web of Science was conducted by two independent authors (December 2012). Randomized clinical trials (RCTs) comparing inhaled TioH versus control (placebo or open control) were included. Data on total mortality were extracted, and missing data were obtained from authors. Relative risk (RR) for total mortality was calculated for each study and pooled. Heterogeneity, the risk of bias, and the publication bias were assessed in accordance with Cochrane's guidance.
  
  
  RESULTS
  Twenty-eight RCTs, evaluating 33,538 patients, met the inclusion criteria. Data were nonheterogeneous, so fixed-effects model analysis was used. The effect of TioH versus placebo was assessed in 19 RCTs, with a total population of 19,826 patients (31,914 patient years), of whom 1,018 died during the study period. A statistically significant decrease in all-cause mortality was associated with the administration of TioH [RR 0.86, 95% confidence interval (CI) 0.76-0.98]. The number needed to treat to prevent one fatality was estimated to be 64 (95% CI 56-110). Comparisons of tiotropium against six more comparators were identified, but the insufficient sample size did not allow robust comparisons with respect to mortality.
  
  
  CONCLUSIONS
  Our meta-analysis of RCTs showed that TioH prolongs the survival of COPD patients compared with placebo. Further RCTs are needed to confirm the potential superiority of prescriptions with versus without TioH in mortality reduction.
authors.affiliation: 1 Respiratory Assembly, Hellenic Society for the Advancement of Biomedical Research , Athens, Greece .
authors.forename: Alexandros G
authors.initials: AG
authors.lastname: Mathioudakis
authors.forename: Prodromos
authors.initials: P
authors.lastname: Kanavidis
authors.forename: Victoria
authors.initials: V
authors.lastname: Chatzimavridou-Grigoriadou
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Gialmanidis
authors.forename: Stavroula G
authors.initials: SG
authors.lastname: Amanetopoulou
authors.forename: Eleni
authors.initials: E
authors.lastname: Christopoulou
authors.forename: Efstathia
authors.initials: E
authors.lastname: Evangelopoulou
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Mathioudakis
mesh_terms: D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011788:Quality of Life; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide