Do Changes of 6-Minute Walk Distance Predict Clinical Events in Patients With Pulmonary Arterial Hypertension? : A Meta-Analysis of 22 Randomized Trials

ObjectivesThe 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).Background6MWD is used as an endpoint to assess the benefit of therapies in PAH. However, whether changes in 6MWD correlate with clinical outcome is unknown.MethodsRandomized 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.ResultsTwenty-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.ConclusionsIn patients with PAH, improvement in 6MWD does not reflect benefit in clinical outcomes.