title: Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension.
abstract: BACKGROUND
  There are currently no licensed medical therapies for inoperable chronic thromboembolic pulmonary hypertension (CTEPH).
  
  
  METHODS
  In this double-blind, placebo-controlled pilot study, 19 subjects with inoperable CTEPH were randomly assigned to sildenafil or placebo for 12 weeks. The primary end point was change in 6-min walking distance (6MWD). Secondary end points included changes in World Health Organization (WHO) class, cardiopulmonary hemodynamics, quality of life (QOL) scores, and N-terminal pro brain natriuretic peptide (NT-proBNP). All subjects were transferred to open-label sildenafil at the end of the study and offered repeat assessment at 12 months.
  
  
  RESULTS
  There were no significant differences between the two groups with respect to change in exercise capacity. However significant improvements were seen in WHO class and pulmonary vascular resistance (PVR). Seventeen subjects were eligible for reassessment at 12 months and demonstrated significant improvements in 6MWD, activity and symptom components of QOL, cardiac index, PVR, and NT-proBNP.
  
  
  CONCLUSIONS
  Although this pilot study was insufficiently powered to test the primary end point, it did suggest beneficial effects in favor of sildenafil in several secondary end points at both 3 months and 12 months. Further larger-scale trials of sildenafil in inoperable CTEPH are required to confirm these findings and potentially increase the treatment options available for this devastating disease.
  
  
  BACKGROUND
  The study protocol was registered with the UK National Research Register database (publication ID N0542136603).
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
authors.forename: Jay
authors.initials: J
authors.lastname: Suntharalingam
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Treacy
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Doughty
authors.affiliation: MRC Biostatistics Unit, Cambridge.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Goldsmith
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
authors.forename: Elaine
authors.initials: E
authors.lastname: Soon
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Toshner
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Sheares
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
authors.forename: Rodney
authors.initials: R
authors.lastname: Hughes
authors.affiliation: University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Morrell
authors.affiliation: Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire. Electronic address: joanna.pepkezaba@papworth.nhs.uk.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pepke-Zaba
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage*; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011687:Purines / Q000008:administration & dosage; D011788:Quality of Life; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate