title: Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials.
abstract: OBJECTIVE
  The objectives of this study were to verify whether improvement in 6-min walk distance (6MWD) is associated with clinical outcome in pulmonary arterial hypertension (PAH).
  
  
  BACKGROUND
  6MWD is used as an endpoint to assess the benefit of therapies in PAH. However, whether changes in 6MWD correlate with clinical outcome is unknown.
  
  
  METHODS
  Randomized trials assessing 6MWD in patients with PAH and reporting clinical endpoints were included in a meta-analysis. The meta-analysis was performed to assess the influence of treatment on outcomes. Meta-regression analysis was performed to test the relationship between 6MWD changes and outcomes.
  
  
  RESULTS
  Twenty-two trials enrolling 3,112 participants were included. Active treatments led to significant reduction of all-cause death (odds ratio [OR]: 0.429; 95% confidence interval [CI]: 0.277 to 0.664; p < 0.01), hospitalization for PAH, and/or lung or heart-lung transplantation (OR: 0.442; 95% CI: 0.309 to 0.632; p < 0.01), initiation of PAH rescue therapy (OR: 0.555; 95% CI: 0.347 to 0.889; p = 0.01), and composite outcome (OR: 0.400; 95% CI: 0.313 to 0.510; p < 0.01). No relationship between 6MWD changes and outcomes was detected.
  
  
  CONCLUSIONS
  In patients with PAH, improvement in 6MWD does not reflect benefit in clinical outcomes.
authors.affiliation: Department of Internal Medicine, Cardiovascular Sciences and Immunology, Federico II University, Via Pansini 5, Naples, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Savarese
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolillo
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Costanzo
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Amore
authors.forename: Milena
authors.initials: M
authors.lastname: Cecere
authors.forename: Teresa
authors.initials: T
authors.lastname: Losco
authors.forename: Francesca
authors.initials: F
authors.lastname: Musella
authors.forename: Paola
authors.initials: P
authors.lastname: Gargiulo
authors.forename: Caterina
authors.initials: C
authors.lastname: Marciano
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents