title: Bosentan therapy for chronic thromboembolic pulmonary hypertension. A national open label study assessing the effect of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study).
abstract: OBJECTIVE
  we performed an open-label national study to evaluate the effects of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (CTEPH).
  
  
  METHODS
  fifteen patients with CTEPH not eligible or waiting for surgery were enrolled. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included quality of life (measured by the Minnesota living with heart failure questionnaire, MLHF), 6 minute walk distance (6MWD), World Health Organization (WHO) functional class, Borg dyspnoea scale, plasma endothelin, serum values of disease severity such as uric acid, N-terminal-pro brain natriuretic peptide (NTproBNP), C-reactive protein measured by a highly sensitive method (CRPs) and other serum and haemodynamic parameters.
  
  
  RESULTS
  after six months of treatment with bosentan, the PVR decreased from 852 (319) to 657(249) dyn*s*m-5 (p = 0.02). Quality of life considerably improved from a mean total score of 48(14) to 35(17) (p = 0.003) with improvements in the physical (from 25(5) to 17(7)) and emotional (from 11(6) to 6(5)) subscores (p = 0.005 and 0.011), respectively. The 6MWD improved from 389(78) to 443(79) meters (p = 0.005). 4 patients (27%) improved and 11 patients (73%) maintained their WHO class with no deterioration during the six months of bosentan treatment (p = 0.02). Uric acid serum levels declined from 525(145) to 453(151) micromol/l (p = 0.006), NTproBNP and CRPs declined insignificantly. Endothelin serum levels increased from 4.3(1.5) to 5.9(2.2) pg/ml (p = 0.025). Patients tolerated the treatment well, and there were no severe adverse events or deaths.
  
  
  CONCLUSIONS
  this open-label study suggests a beneficial effect of bosentan therapy not only on pulmonary haemodynamics, but also on quality of life and exercise capacity for patients with severe CTEPH.
authors.affiliation: Clinics of Internal Medicine, Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland. silvia.ulrich@usz.ch
authors.forename: Silvia
authors.initials: S
authors.lastname: Ulrich
authors.forename: Rudolf
authors.initials: R
authors.lastname: Speich
authors.forename: Guido
authors.initials: G
authors.lastname: Domenighetti
authors.forename: Thomas
authors.initials: T
authors.lastname: Geiser
authors.forename: John-David
authors.initials: JD
authors.lastname: Aubert
authors.forename: Thierry
authors.initials: T
authors.lastname: Rochat
authors.forename: Lars
authors.initials: L
authors.lastname: Huber
authors.forename: Ursula
authors.initials: U
authors.lastname: Treder
authors.forename: Mannuel
authors.initials: M
authors.lastname: Fischler
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D002908:Chronic Disease; D065128:Endothelin Receptor Antagonists; D017079:Exercise Tolerance; D005260:Female; D006305:Health Status Indicators; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan