Association between six-minute walk distance and long-term outcomes in patients with pulmonary arterial hypertension: Data from the randomized SERAPHIN trial

• Published in: PloS one Vol. 13; no. 3; p. e0193226
• Main Authors: Souza, Rogério, Channick, Richard N., Delcroix, Marion, Galiè, Nazzareno, Ghofrani, Hossein-Ardeschir, Jansa, Pavel, Le Brun, Franck-Olivier, Mehta, Sanjay, Perchenet, Loïc, Pulido, Tomás, Sastry, B. K. S., Sitbon, Olivier, Torbicki, Adam, Rubin, Lewis J., Simonneau, Gérald
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.03.2018; Public Library of Science (PLoS)
• Subjects: Analysis; Biology and Life Sciences; Care and treatment; Health aspects; Life Sciences; Medicine and Health Sciences; Patient outcomes; Prognosis; Pulmonary hypertension; Treatment outcome; Walking
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193226

Patients with pulmonary arterial hypertension who achieve a six-minute walk distance of 380-440 m may have improved prognosis. Using the randomized controlled trial of macitentan in pulmonary arterial hypertension (SERAPHIN), the association between six-minute walk distance and long-term outcomes was explored. Patients with six-minute walk distance data at Month 6 were dichotomized as above or below the median six-minute walk distance (400 m) and assessed for future risk of pulmonary arterial hypertension-related death or hospitalization and all-cause death. Additionally, six-minute walk distance values at baseline, Month 6 and the change from baseline to Month 6 were categorized by quartiles. All associations were analyzed by the Kaplan-Meier method using a log-rank test and Cox regression models. Patients with a six-minute walk distance >400 m vs. ≤400 m at Month 6 have a reduced risk of pulmonary arterial hypertension-related death or hospitalization (hazard ratio 0.48; 95% confidence interval 0.33-0.69). The risk was also lower for patients with higher quartiles of six-minute walk distance at baseline or Month 6 (baseline: hazard ratio [Q4 (>430 m) vs. Q1 (≤300 m)] 0.23; 95% confidence interval 0.15-0.36; Month 6: hazard ratio [Q4 (>455 m) vs. Q1 (≤348 m)] 0.33; 95% confidence interval 0.19-0.55). In contrast, six-minute walk distance changes at Month 6 were not associated with the risk of pulmonary arterial hypertension-related death or hospitalization (p = 0.477). These findings were consistent when adjusted for known confounders. Similar results were observed for the risk of all-cause death up to end of study. Patients with pulmonary arterial hypertension walking >400 m had better long-term prognosis. Although changes in six-minute walk distance were not associated with long-term outcomes, assessing absolute six-minute walk distance values remains important in the clinical management of patients with pulmonary arterial hypertension.