title: Effects of oral treatments on clinical outcomes in pulmonary arterial hypertension: A systematic review and meta-analysis.
abstract: BACKGROUND
  Many targeted therapies have been approved for pulmonary arterial hypertension (PAH), most of which are in oral forms. However, the effects of these drugs on lifesaving are unclear. Our objective was to evaluate the effects of oral treatments on clinical outcomes especially all-cause mortality in patients with PAH.
  
  
  METHODS
  MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for relevant articles up to April 2014. Randomized, double-blind, parallel-group clinical trials that compared oral agents with placebo were selected. Data for populations, interventions, and outcomes were extracted independently by 2 investigators, and disagreements were resolved by consensus. Quality assessment was performed using the Cochrane risk-of-bias tool.
  
  
  RESULTS
  Twenty-one randomized, controlled, clinical trials involving 5105 patients were identified in the primary analysis. The overall estimated odds ratio (OR) of combined clinical worsening (CCW) events between active treatment groups and control groups was 0.55 (95% CI 0.47-0.64, P < .001). However, the effect of oral treatments on reducing all-cause mortality was not statistically significant (OR 0.82, 95% CI 0.61-1.10, P = .192), which was consistent for approved drugs (OR 0.84, 95% CI 0.61-1.18, P = .316) and drugs that were not approved (OR 0.72, 95% CI 0.36-1.44, P = .352). In the sensitivity analysis, a significant reduction was achieved in CCW events (P < .001) but not in all-cause mortality (P = .057).
  
  
  CONCLUSIONS
  This pooled analysis shows the benefits of oral treatments on CCW events in patients with PAH. However, these drugs seem to exhibit less favorable effects on life expectancy in the short-term follow-up, suggesting further evaluation is required.
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Hong-Da
authors.initials: HD
authors.lastname: Zhang
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Dan-Chen
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China. Electronic address: jingzhicheng@vip.163.com.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D000284:Administration, Oral; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use*; D005080:Exercise Test; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality; D000068877:Imatinib Mesylate; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D011453:Prostaglandins / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D001549:Benzamides; D065128:Endothelin Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011453:Prostaglandins; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D014665:Vasodilator Agents; C112331:terbogrel; D000068877:Imatinib Mesylate; C542595:riociguat