title: Bosentan for chronic thromboembolic pulmonary hypertension: findings from a systematic review and meta-analysis.
abstract: BACKGROUND
  After acute pulmonary embolism, chronic thromboembolic pulmonary hypertension (CTEPH) is diagnosed in about 1% of patients. We performed a systematic review and meta-analysis aimed at assessing the effects of bosentan therapy in patients with CTEPH.
  
  
  METHODS
  We searched in MEDLINE and Embase using the terms 'pulmonary hypertension' AND 'bosentan'. Papers were included in this review if they reported on patients with objectively confirmed CTEPH treated with bosentan. Efficacy measures were the improvement in NYHA class, in 6 minute walking distance (6 mwd) and in hemodynamics (cardiac index, pulmonary artery pressure, pulmonary vascular resistance). Mortality and safety were also assessed.
  
  
  RESULTS
  Overall, 543 papers were found. Eight single-arm cohort studies (175 patients), one randomized double-blind study, one case-control study and one case report were included in the analysis. A 35.9 meters weighted mean increase in 6 minute walking distance was observed after 3-6 months of treatment (9 studies, 208 patients) (95% CI 33.6 to 38.2; p<0.001) and an additional increase of 21 meters after one year (4 studies, 80 patients). About 25% of patients had an improvement on functional NYHA class at 3-6 months. Data on hemodynamics were available in seven studies, 185 patients. The mean weighted increase in cardiac index at 3-6 months was 0.23 l/min/m2 (95% CI 0.22 to 0.25); the mean weighted decrease in pulmonary artery pressure at 3-6 months was 2.62 mmHg (95% CI 2.44 to 2.80). Three patient died within 3-6 months (1.4%) and 3 additional patients died within one year.
  
  
  CONCLUSIONS
  Bosentan therapy is associated with an improvement of hemodynamics and probably exercise capacity in patients with CTEPH. Controlled data on mortality and time to clinical worsening in patients with CTEPH are needed.
authors.affiliation: Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy. cecilia.becattini@unipg.it
authors.forename: Cecilia
authors.initials: C
authors.lastname: Becattini
authors.forename: Giorgia
authors.initials: G
authors.lastname: Manina
authors.forename: Chiara
authors.initials: C
authors.lastname: Busti
authors.forename: Silvia
authors.initials: S
authors.lastname: Gennarini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan