1. Do Changes of 6-minute Walk Distance Predict Clinical Events in Patients with Pulmonary Arterial Hypertension? A Meta-analysis Of 22 Randomized Trials
Gianluigi Savarese, MD, Stefania Paolillo, MD, Pierluigi Costanzo, MD, Carmen D’Amore, MD, Milena Cecere, MD, Teresa Losco, MD, Francesca Musella, MD, Paola Gargiulo, MD, Caterina Marciano, MD, Pasquale Perrone-Filardi, MD, PhD

2. Objective
To verify whether improvement in 6-minute walk distance (6MWD) is associated with clinical outcome in pulmonary arterial hypertension (PAH).
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3. Background
6MWD is used as end-point to assess the benefit of therapies in PAH.
However, whether changes in 6MWD correlate with clinical outcome is unknown.
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4. Methods
Randomized trials in PAH patients assessing 6MWD and reporting clinical end- points were included in a meta-analysis.
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.
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5. Results 22 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, CI: to 0.632, p<0.01),
initiation of PAH rescue therapy
(OR:0.555, CI:0.347 to 0.889, p=0.01) and
composite outcome
(OR:0.400, CI:0.313 to 0.510, p<0.01).
No relationship between 6MWD changes and outcomes was detected.
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6. OR estimate of composite outcome in active treatment groups compared with control groups
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7. Meta-regression between Δ6MWD and composite outcome (A), all-cause death (B), hospitalization for PAH and/or lung or heart-lung transplantation (C) and initiation of PAH rescue therapy (D).
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8. Conclusion
In patients with PAH, improvement in 6MWD does not reflect reduction in clinical outcomes.
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