title: Comparative effectiveness and safety of drug therapy for pulmonary arterial hypertension: a systematic review and meta-analysis.
abstract: BACKGROUND
  Current treatments for pulmonary arterial hypertension (PAH) have been shown to improve dyspnea, 6-min walk distance (6MWD), and pulmonary hemodynamics, but few studies were designed to compare treatment regimens or assess the impact of treatment on mortality.
  
  
  METHODS
  We conducted a systematic review to evaluate the comparative effectiveness and safety of monotherapy or combination therapy for PAH using endothelin receptor antagonists, phosphodiesterase inhibitors, or prostanoids. We searched English-language publications of comparative studies that reported intermediate or long-term outcomes associated with drug therapy for PAH. Two investigators abstracted data and rated study quality and applicability.
  
  
  RESULTS
  We identified 28 randomized controlled trials involving 3,613 patients. We found no studies that randomized treatment-naive patients to monotherapy vs combination therapy. There was insufficient statistical power to detect a mortality difference associated with treatment. All drug classes demonstrated increases in 6MWD when compared with placebo, and combination therapy showed improved 6MWD compared with monotherapy. For hospitalization, the OR was lower in patients taking endothelin receptor antagonists or phosphodiesterase-5 inhibitors compared with placebo (OR, 0.34 and 0.48, respectively).
  
  
  CONCLUSIONS
  Although no studies were powered to detect a mortality reduction, monotherapy was associated with improved 6MWD and reduced hospitalization rates. Our findings also suggest an improvement in 6MWD when a second drug is added to monotherapy.
authors.affiliation: Department of Community and Family Medicine, Duke University School of Medicine; Duke Evidence-based Practice Center, Duke Clinical Research Institute, Duke University. Electronic address: remy.coeytaux@dm.duke.edu.
authors.forename: Remy R
authors.initials: RR
authors.lastname: Coeytaux
authors.affiliation: Department of Community and Family Medicine, Duke University School of Medicine.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Schmit
authors.affiliation: Division of Pulmonary Medicine, Duke University School of Medicine.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Kraft
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University School of Medicine.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Kosinski
authors.affiliation: United States Navy, Department of Medicine, Duke University Medical Center.
authors.forename: Alicea M
authors.initials: AM
authors.lastname: Mingo
authors.affiliation: Division of Hospital Medicine, Department of Medicine, Duke University Medical Center.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Vann
authors.affiliation: Division of Pulmonary Medicine, Duke University School of Medicine.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gilstrap
authors.affiliation: Division of Pulmonary Medicine, Duke University School of Medicine.
authors.forename: C William
authors.initials: CW
authors.lastname: Hargett
authors.affiliation: Duke Evidence-based Practice Center, Duke Clinical Research Institute, Duke University.
authors.forename: Brooke
authors.initials: B
authors.lastname: Heidenfelder
authors.affiliation: Duke Evidence-based Practice Center, Duke Clinical Research Institute, Duke University; Division of General Internal Medicine, Department of Medicine, Duke University Medical Center; Center for Health Services Research in Primary Care, Department of Veterans Affairs, Durham, NC.
authors.forename: Rowena J
authors.initials: RJ
authors.lastname: Dolor
authors.affiliation: Duke Evidence-based Practice Center, Duke Clinical Research Institute, Duke University; Division of General Internal Medicine, Department of Medicine, Duke University Medical Center; Center for Health Services Research in Primary Care, Department of Veterans Affairs, Durham, NC.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: McCrory
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D065627:Familial Primary Pulmonary Hypertension; D014943:Global Health; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011453:Prostaglandins / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects / Q000502:physiology*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors; D011453:Prostaglandins