Document Detail

Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for pulmonary arterial hypertension: a placebo-controlled trial.
MedLine Citation:
PMID:  20022264     Owner:  NLM     Status:  MEDLINE    
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.
Jagdish Hiremath; Sadagopa Thanikachalam; Keyur Parikh; Somasundaram Shanmugasundaram; Sudhakar Bangera; Leland Shapiro; Gregory B Pott; Cindy L Vnencak-Jones; Carl Arneson; Michael Wade; R James White;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  29     ISSN:  1557-3117     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-05-27     Revised Date:  2010-07-15    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  137-49     Citation Subset:  IM    
Ruby Hall Clinic, Pune, India.
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MeSH Terms
Antihypertensive Agents / administration & dosage*
Biological Markers / blood
Double-Blind Method
Epoprostenol / administration & dosage,  analogs & derivatives*
Hypertension, Pulmonary / drug therapy*
Infusions, Intravenous
Middle Aged
Physical Endurance / drug effects*
Severity of Illness Index
Treatment Outcome
Reg. No./Substance:
0/Antihypertensive Agents; 0/Biological Markers; 0/treprostinil; 35121-78-9/Epoprostenol
B Brundage / ; D Langleben / ; S Rich / ; G Koch / ; T Wenger / ; P G Kerkar / ; P R K Jain / ; P V Suresh / ; R Babu / ; Y Kumble / ; C Raghu / ; V S Ramachandra / ; P Ramachandran / ; S Tyagi / ; S Ramasubban / ; M V Kumar / ; S W Gheyee / ; R Kelen / ; S McSwain / ; R Jeffs / ; D Bunce / ; J Sigman / ; W DellaMaestra / ; C Greene /
Comment In:
J Heart Lung Transplant. 2010 Jul;29(7):825-6   [PMID:  20456982 ]
J Heart Lung Transplant. 2010 Feb;29(2):157-8   [PMID:  20113908 ]

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