Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for pulmonary arterial hypertension: a placebo-controlled trial.
BACKGROUND
Pulmonary arterial hypertension (PAH) remains a poorly understood and frequently lethal disease with few treatment options.


METHODS
We conducted a placebo-controlled trial of intravenous treprostinil, a prostacyclin analog, in treatment-naive PAH patients. During 12 weeks of treatment with treprostinil or placebo, we quantified 6-minute walk distance (6MW), clinical symptoms and 11 cytokines/growth factors.


RESULTS
Forty-two of 44 study patients had idiopathic/familial PAH in New York Heart Association (NYHA) Class III. Treprostinil increased 6MW by a placebo-corrected median of 83 meters (p = 0.008; mean increase 93 +/- 42 meters), reduced Borg score by a median 2.0 units (p = 0.02), and improved NYHA class by a median of 1.0 (p = 0.02). There was a trend toward improved survival with treprostinil (p = 0.051). Baseline plasma angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and platelet-derived growth factor (PDGF) were elevated compared with reported normal ranges. Treatment with treprostinil was associated with decreased Ang-2 levels. Improvement in 6MW distance after treatment was associated with reductions in Ang-2 and MMP-9 levels. Most of the cytokines and growth factors studied were not abnormal with disease nor did they change with treatment.


CONCLUSIONS
We conclude that treprostinil treatment significantly improved exercise capacity, dyspnea and functional class. Several plasma proteins that might track disease were abnormal at baseline, and changes were associated with improved exercise capacity.
Hiremath
Jagdish
J
Ruby Hall Clinic, Pune, India.
Thanikachalam
Sadagopa
S
Parikh
Keyur
K
Shanmugasundaram
Somasundaram
S
Bangera
Sudhakar
S
Shapiro
Leland
L
Pott
Gregory B
GB
Vnencak-Jones
Cindy L
CL
Arneson
Carl
C
Wade
Michael
M
White
R James
RJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015444:Exercise; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010807:Physical Endurance / Q000187:drug effects*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016138:Walking
D000959:Antihypertensive Agents; D015415:Biomarkers; D011464:Epoprostenol; C427248:treprostinil