title: Endothelin receptor antagonists for pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension is a devastating disease, which leads to right heart failure and premature death. Recent evidence suggests that endothelin receptor antagonists may be promising drugs in the treatment of pulmonary arterial hypertension.
  
  
  OBJECTIVE
  To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension.
  
  
  METHODS
  We searched CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of January 2012.
  
  
  METHODS
  We included randomised trials (RCTs) and quasi-randomised trials involving patients with pulmonary arterial hypertension.
  
  
  METHODS
  Five review authors independently selected studies, assessed study quality and extracted data.
  
  
  RESULTS
  We included 12 randomised controlled trials involving 1471 patients. All the trials were of relatively short duration (12 weeks to six months). After treatment, patients treated with endothelin receptor antagonists could walk on average 33.71 metres (95% confidence interval (CI) 24.90 to 42.52 metres) further than those treated with placebo in a six-minute walk test. Endothelin receptor antagonists improved more patients' World Health Organization/New York Heart Association (WHO/NYHA) functional class status than placebo (odds ratio (OR) 1.60; 95% CI 1.20 to 2.14), and reduced the odds of functional class deterioration compared with placebo (OR 0.26; 95% CI 0.16 to 0.42). There was a reduction in mortality that did not reach statistical significance on endothelin receptor antagonists (OR 0.57; 95% CI 0.26 to 1.24), and limited data suggest that endothelin receptor antagonists improve the Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients. Hepatic toxicity was not common, and endothelin receptor antagonists were well tolerated in this population. However, several cases of irreversible liver failure caused by sitaxsentan have been reported that led to license holder for sitaxsentan to withdraw the product from all markets worldwide.
  
  
  CONCLUSIONS
  Endothelin receptor antagonists can increase exercise capacity, improve WHO/NYHA functional class, prevent WHO/NYHA functional class deterioration, reduce dyspnoea and improve cardiopulmonary haemodynamic variables in patients with pulmonary arterial hypertension with WHO/NYHA functional class II and III. However, there was only a trend towards endothelin receptor antagonists reducing mortality in patients with pulmonary arterial hypertension. Efficacy data are strongest in those with idiopathic pulmonary hypertension. The irreversible liver failure caused by sitaxsentan and its withdrawal from global markets emphasise the importance of hepatic monitoring in patients treated with endothelin receptor antagonists.
authors: The First Hospital of Hebei Medical University, Shijiazhuang, China. dr_chaoliu@yahoo.com.cn. lcwv@sohu.com.
authors: Chao
authors: C
authors: Liu
authors: Junmin
authors: J
authors: Chen
authors: Yanqiu
authors: Y
authors: Gao
authors: Bao
authors: B
authors: Deng
authors: Kunshen
authors: K
authors: Liu
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D065128:Endothelin Receptor Antagonists; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists