title: Oral targeted therapies in the treatment of pulmonary arterial hypertension: a meta-analysis of clinical trials.
abstract: BACKGROUND
  Oral targeted therapies have been widely used in the treatment of pulmonary arterial hypertension (PAH). Many new oral agents emerge for PAH in recent years. In this study, we performed a meta-analysis to evaluate the efficacy and safety of oral targeted therapies in PAH, focusing on overall survival improvement.
  
  
  METHODS
  Randomized controlled trials of oral targeted therapies in patients with PAH published through September 2013 were identified by searching the Cochrane Library, EMBASE, and PUBMED databases. We calculated risk ratios for dichotomous data and weighted mean differences with 95% confidence intervals for continuous data.
  
  
  RESULTS
  18 trials with a total of 4363 subjects were indentified in the meta-analysis. Analysis by drug class revealed that phosphodiesterase type 5 inhibitors (PDE-5Is) were associated with a statically significant reduction in mortality (RR 0.22; 95% CI 0.07-0.71, p = 0.011), while other drugs only showed a trend toward reducing mortality. Compared with placebo, endothelin receptor antagonists (ERAs), PDE-5Is and riociguat significantly reduced clinical worsening, ameliorated WHO function class, and increased the 6-min walk distance. However, oral prostanoids only showed a mild effect on 6-min walk distance (19.88 m; 95% CI 10.12-29.64, p = 0.000), and did not have any effect on reducing mortality and clinical worsening. Moreover, oral prostanoids significantly increased the incidence of withdrawal due to adverse effects (RR 3.41; 95% CI 2.06-5.63, p = 0.000).
  
  
  CONCLUSIONS
  This meta-analysis suggests that all oral agents confer a therapeutic benefit. Of these, only PDE-5Is has a proven survival benefit. ERAs and riociguat are efficient in reducing clinical worsening, and ameliorating exercise capacity. Oral prostanoids have the significant adverse effects and weak therapeutic effects.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China. Electronic address: zhengyaguo@126.com.
authors.forename: Ya-Guo
authors.initials: YG
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
authors.forename: En-Ci
authors.initials: EC
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China. Electronic address: xiongcm2000@163.com.
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Xiong
mesh_terms: D000284:Administration, Oral; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors
keywords: Endothelin receptor antagonists; Meta-analysis; Phosphodiesterase 5 inhibitors; Prostanoids; Pulmonary arterial hypertension; Randomized controlled trials