Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials

J Am Coll Cardiol. 2012 Sep 25;60(13):1192-201. doi: 10.1016/j.jacc.2012.01.083.


Objectives: 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.

Publication types

  • Meta-Analysis

MeSH terms

  • Antihypertensive Agents / administration & dosage
  • Exercise Test
  • Exercise Tolerance / physiology
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / physiopathology*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Walking / physiology*


  • Antihypertensive Agents