title: Comparative efficacy and acceptability of endothelin receptor antagonists for pulmonary arterial hypertension: A network meta-analysis.
abstract: BACKGROUND
  Endothelin receptor antagonists (ERAs) such as ambrisentan, sitaxsentan, bosentan and macitentan are primary drug therapies for pulmonary arterial hypertension (PAH) patients. However, the optimal drugs for PAH remained controversial due to heterogeneous nature of randomized control trials (RCTs).
  
  
  METHODS
  Apart from traditional meta-analysis, network meta-analysis (NMA) was performed in this study for multiple comparisons among PAH therapies. The 6 minute walking distance (6MWD) and clinical worsening were efficacy outcomes whereas serious adverse effects (SAE) and all-cause discontinuation were acceptability outcomes. The weighted mean difference (WMD) and odds ratio (OR) along with their 95% confidence interval (95% CI) or 95% credible interval (95% CrI) were used to evaluate the positive and negative effects of these therapies on PAH patients.
  
  
  RESULTS
  By synthesizing direct evidence from 10 studies with a total number of 2172 patients, we discovered that all of the four PAH therapies significantly increased the average 6MWD in comparison to the placebo (P-value<0.05). Moreover, bosentan and ambrisentan both showed significant association with a decrease in the risk of clinical worsening compared to placebo. Regarding of all-cause discontinuation, ambrisentan is the only therapy which was significantly associated with a risk decrease compared to placebo. However, there was no sufficient evidence suggesting significant difference in any efficacy or acceptability outcomes between any two of the PAH therapies (P-value>0.05).
  
  
  CONCLUSIONS
  Ambrisentan could be considered as the most appropriate therapy among the four ERAs for PAH patients. Bosentan also behaved well, but it is not as safe as ambrisentan.
authors.affiliation: Department of Medicine, Shigatse People's Hospital, Shigatse 857000, China.
authors.forename: Mi-Ma
authors.initials: MM
authors.lastname: Duo-Ji
authors.affiliation: Department of Medicine, Shigatse People's Hospital, Shigatse 857000, China; Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center, Building 3, No. 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, No. 138 Yixueyuan Road, Shanghai 200032, China. Electronic address: baerriza82@163.com.
authors.forename: Zi-Wen
authors.initials: ZW
authors.lastname: Long
mesh_terms: D016903:Drug Monitoring / Q000379:methods; D065128:Endothelin Receptor Antagonists / Q000145:classification / Q000494:pharmacology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D010666:Phenylpropionates / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D000070857:Walk Test / Q000379:methods
chemical_list: D065128:Endothelin Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan
keywords: Endothelin receptor antagonists; Network meta-analysis; Pulmonary arterial hypertension