title: Endothelin receptor antagonist therapy in congenital heart disease with shunt-associated pulmonary arterial hypertension: a qualitative systematic review.
abstract: BACKGROUND
  Congenital heart disease (CHD) with systemic-topulmonary shunting is associated with pulmonary arterial hypertension (PAH). There are similar clinical and pathophysiological features between CHD with shunt-associated PAH and idiopathic PAH. Endothelin-receptor antagonists (ERAs) are oral medications that improve pulmonary hemodynamics, symptoms and functional capacity in many PAH patients. However, the role of ERAs in CHD with shunt-associated PAH is unclear.
  
  
  METHODS
  MEDLINE, EMBASE and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases were searched for articles published from 1966 through September 2006, as well as bibliographies of all retrieved papers. All published English-language studies of adult CHD patients with shunt-associated PAH treated with ERAs were reviewed for clinical, functional and hemodynamic outcomes.
  
  
  RESULTS
  Ten studies of 174 adult CHD subjects with shunt-associated PAH were identified. Other than one placebo-controlled, randomized clinical trial, all studies were open-label, uncontrolled observational trials. Subjects were treated with the ERA bosentan for a mean (+/- SD) of 9+/-7 months. Nine studies reported improved World Health Organization (WHO) modification of the New York Heart Association functional class, with 95 of 164 subjects (58%) improving by at least one functional class. The 6 min walk distance improved in all eight studies in which it was assessed. Bosentan was generally well tolerated; 2.3% of subjects withdrew because of elevated liver enzymes. Two patients with WHO functional class IV PAH died during bosentan therapy.
  
  
  CONCLUSIONS
  Treatment of CHD patients with shunt-associated PAH with the ERA bosentan is associated with an improvement in functional class and objectively measured exercise capacity. The consistency of the uncontrolled data and the positive results of a single randomized clinical trial suggest a role for ERA therapy in CHD patients with shunt-associated PAH. Caution is suggested when considering bosentan therapy for CHD patients with WHO functional class IV PAH.
authors.affiliation: Department of Medicine, University of Western Ontario, London, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Fine
authors.forename: B
authors.initials: B
authors.lastname: Dias
authors.forename: G
authors.initials: G
authors.lastname: Shoemaker
authors.forename: S
authors.initials: S
authors.lastname: Mehta
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000077300:Bosentan; D004541:Eisenmenger Complex / Q000150:complications / Q000188:drug therapy; D065128:Endothelin Receptor Antagonists; D005080:Exercise Test; D006330:Heart Defects, Congenital / Q000150:complications* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011652:Pulmonary Circulation; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan