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

• Published in: The Journal of heart and lung transplantation Vol. 31; no. 8; pp. 811 - 816
• Main Authors: Frantz, Robert P., MD, McDevitt, Susanne, RN, MSN, Walker, Susan, MS
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2012; Elsevier
• Subjects: 6-minute walk distance; Administration, Inhalation; Adolescent; Adult; Aged; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - therapeutic use; Biological and medical sciences; biomarker; Biomarkers - blood; Cardiology. Vascular system; Double-Blind Method; Epoprostenol - administration & dosage; Epoprostenol - analogs & derivatives; Epoprostenol - therapeutic use; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary - blood; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - physiopathology; inhaled treprostinil; Male; Medical sciences; Middle Aged; N-terminal pro–B-type natriuretic peptide; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; Pneumology; Predictive Value of Tests; pulmonary arterial hypertension; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Severity of Illness Index; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Time Factors; Treatment Outcome; Walking - physiology; Young Adult; inhaled treprostinil; biomarker; 6-minute walk distance; N-terminal pro–B-type natriuretic peptide; pulmonary arterial hypertension; Human; Vasodilator agent; Prostaglandin I2; Respiratory disease; Cardiovascular disease; Patient; Change; Phlebology; Artery; Pulmonary hypertension; Inhalation; Treprostinil; Circulatory system; Cardiology; Distance
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2012.04.005

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.