title: Does the outcome justify an oral-first treatment strategy for management of pulmonary arterial hypertension?
abstract: BACKGROUND
  Guidelines for the treatment of World Health Organization (WHO) functional class (FC) III pulmonary arterial hypertension (PAH) provide for oral (PO) therapy or parenteral prostacyclins at the discretion of expert physicians. The objective of this study was to assess the appropriateness of PO-first treatment in patients with WHO FC III PAH.
  
  
  METHODS
  This study was a retrospective analysis of 79 treatment-naive adult patients with idiopathic, familial, or anorexigen-associated PAH, referred to a single pulmonary hypertension center. Forty-eight received either PO therapy with an endothelin receptor antagonist, calcium channel blocker, or phosphodiesterase inhibitor (PO group) and 31 an IV or subcutaneous (SC) prostacyclin (IV/SC group).
  
  
  RESULTS
  Patients in the IV/SC group had a significantly worse baseline hemodynamic profile; however, on univariate analysis, there was no association between hemodynamics and mortality. Initial treatment with PO vs IV/SC therapy was associated with a lower overall mortality (20.8% vs 45.2%, P = .02) and a lower 5-year mortality (14.6% vs 32.3%, P = .062). Based on the National Institutes of Health equation, actual survival for patients who received PO therapy was greater than predicted at 5 years. Finally, there were similar improvements between groups in 6-min walk distance (P = .38) at 6 to 12 months after initiation of treatment.
  
  
  CONCLUSIONS
  For WHO FC III PAH that is idiopathic, familial, or anorexigen associated, the clinical decision for treatment with a PO-first strategy is associated with a high survival rate when patients are appropriately risk stratified prior to initiation of therapy. The more potent prostacyclins can be reserved for high-risk patients, those with evidence of disease progression, or those with treatment failure.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: William K
authors.initials: WK
authors.lastname: Cornwell
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Vallerie V
authors.initials: VV
authors.lastname: McLaughlin
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Sangeetha M
authors.initials: SM
authors.lastname: Krishnan
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI. Electronic address: mrubenfi@med.umich.edu.
authors.forename: Melvyn
authors.initials: M
authors.lastname: Rubenfire
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001067:Appetite Depressants / Q000009:adverse effects; D002121:Calcium Channel Blockers / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000601:surgery; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D001067:Appetite Depressants; D002121:Calcium Channel Blockers