TY - JOUR
T1 - Baseline NT-proBNP correlates with change in 6-minute walk distance in patients with pulmonary arterial hypertension in the pivotal inhaled treprostinil study TRIUMPH-1
AU - Frantz, Robert P.
AU - McDevitt, Susanne
AU - Walker, Susan
N1 - Funding Information:
R.P.F. has served on advisory boards for United Therapeutics Corporation (UTC) without personal financial gain, aside from coverage for travel expenses, in keeping with the Mayo Clinic's conflict-of-interest policy for clinical investigators. He has received research funding from UTC for unrelated research projects and has also received educational grants from UTC , without personal financial gain. S.M. and S.W. are employees of UTC. Assistance with medical writing and editing was provided under the direction of the authors by Pratibha Hebbar and Chris Lawrence, MedThink Communications, with support from UTC. UTC also provided support for data collection, data management and statistical analysis. S.M. and S.W. are employees of UTC and as study investigators were involved in data interpretation and had the right to approve or disapprove publication of the finished manuscript.
PY - 2012/8
Y1 - 2012/8
N2 - Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of disease severity in pulmonary arterial hypertension (PAH). In this study we aimed to determine whether baseline NT-proBNP levels correlate with improvement in 6-minute walk distance (6MWD) in the pivotal randomized, placebo-controlled, double-blind study of the addition of inhaled treprostinil to oral therapy for PAH. Methods: A post hoc analysis of data from the TRIUMPH-1 study was performed in patients who had assessments of NT-proBNP levels and baseline and Week 12 6MWD. Least-squares mean analysis was used to compare patients in the highest quartile of baseline NT-proBNP with those in lower quartiles with regard to change from baseline in 6MWD, stratified by treatment. Results: The NT-proBNP within-treatment median changes from baseline to Week 12 were +44 and -72 pg/ml, and the median changes in 6MWD from baseline to Week 12 were +5 and +40 m for the placebo (n = 94) and inhaled treprostinil (n = 84) groups, respectively. Baseline NT-proBNP levels demonstrated a strong interaction with treatment in predicting change from baseline for 6MWD (p < 0.01), indicating that, in the upper quartile (<1,513.5 pg/ml), patients on inhaled treprostinil had a better response (+64 vs +32 m), whereas patients on placebo fared worse (-13 vs +20 m) when compared with the lower 3 quartiles (<1,513.5 pg/ml). Furthermore, least-squares mean difference in 6MWD between active and placebo groups was +67 and +16 m for the upper and lower 3 quartiles of NT-proBNP, respectively. Conclusions: Greater improvement in 6MWD in actively treated patients with high levels of NT-proBNP enhances understanding of the robustness of clinical response to inhaled treprostinil in more advanced disease.
AB - Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of disease severity in pulmonary arterial hypertension (PAH). In this study we aimed to determine whether baseline NT-proBNP levels correlate with improvement in 6-minute walk distance (6MWD) in the pivotal randomized, placebo-controlled, double-blind study of the addition of inhaled treprostinil to oral therapy for PAH. Methods: A post hoc analysis of data from the TRIUMPH-1 study was performed in patients who had assessments of NT-proBNP levels and baseline and Week 12 6MWD. Least-squares mean analysis was used to compare patients in the highest quartile of baseline NT-proBNP with those in lower quartiles with regard to change from baseline in 6MWD, stratified by treatment. Results: The NT-proBNP within-treatment median changes from baseline to Week 12 were +44 and -72 pg/ml, and the median changes in 6MWD from baseline to Week 12 were +5 and +40 m for the placebo (n = 94) and inhaled treprostinil (n = 84) groups, respectively. Baseline NT-proBNP levels demonstrated a strong interaction with treatment in predicting change from baseline for 6MWD (p < 0.01), indicating that, in the upper quartile (<1,513.5 pg/ml), patients on inhaled treprostinil had a better response (+64 vs +32 m), whereas patients on placebo fared worse (-13 vs +20 m) when compared with the lower 3 quartiles (<1,513.5 pg/ml). Furthermore, least-squares mean difference in 6MWD between active and placebo groups was +67 and +16 m for the upper and lower 3 quartiles of NT-proBNP, respectively. Conclusions: Greater improvement in 6MWD in actively treated patients with high levels of NT-proBNP enhances understanding of the robustness of clinical response to inhaled treprostinil in more advanced disease.
KW - 6-minute walk distance
KW - N-terminal pro-B-type natriuretic peptide
KW - biomarker
KW - inhaled treprostinil
KW - pulmonary arterial hypertension
UR - http://www.scopus.com/inward/record.url?scp=84863320780&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863320780&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2012.04.005
DO - 10.1016/j.healun.2012.04.005
M3 - Article
C2 - 22759797
AN - SCOPUS:84863320780
SN - 1053-2498
VL - 31
SP - 811
EP - 816
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 8
ER -