title: Beraprost therapy for pulmonary arterial hypertension.
abstract: OBJECTIVE
  The purpose of this study was to assess the safety and efficacy of the oral prostacyclin analogue beraprost sodium during a 12-month double-blind, randomized, placebo-controlled trial in patients with pulmonary arterial hypertension (PAH).
  
  
  BACKGROUND
  Pulmonary arterial hypertension is a progressive disease that ultimately causes right heart failure and death. Despite the risks from its delivery system, continuous intravenous epoprostenol remains the most efficacious treatment currently available.
  
  
  METHODS
  A total of 116 patients with World Health Organization (WHO) functional class II or III primary pulmonary hypertension or PAH related to either collagen vascular diseases or congenital systemic to pulmonary shunts were enrolled. Patients were randomized to receive the maximal tolerated dose of beraprost sodium (median dose 120 microg four times a day) or placebo for 12 months. The primary end point was disease progression; i.e., death, transplantation, epoprostenol rescue, or >25% decrease in peak oxygen consumption (VO(2)). Secondary end points included exercise capacity assessed by 6-min walk test and peak VO(2), Borg dyspnea score, hemodynamics, symptoms of PAH, and quality of life.
  
  
  RESULTS
  Patients treated with beraprost exhibited less evidence of disease progression at six months (p = 0.002), but this effect was not evident at either shorter or longer follow-up intervals. Similarly, beraprost-treated patients had improved 6-min walk distance at 3 months by 22 m from baseline and at 6 months by 31 m (p = 0.010 and 0.016, respectively) compared with placebo, but not at either 9 or 12 months. Drug-related adverse events were common and were related to the disease and/or expected prostacyclin adverse events.
  
  
  CONCLUSIONS
  These data suggest that beneficial effects may occur during early phases of treatment with beraprost in WHO functional class II or III patients but that this effect attenuates with time.
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. rjb3@columbia.edu
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Michael
authors.initials: M
authors.lastname: McGoon
authors.forename: Vallerie
authors.initials: V
authors.lastname: McLaughlin
authors.forename: Victor
authors.initials: V
authors.lastname: Tapson
authors.forename: Stuart
authors.initials: S
authors.lastname: Rich
authors.forename: Lewis
authors.initials: L
authors.lastname: Rubin
authors.forename: Karlman
authors.initials: K
authors.lastname: Wasserman
authors.forename: Ronald
authors.initials: R
authors.lastname: Oudiz
authors.forename: Shelley
authors.initials: S
authors.lastname: Shapiro
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Robbins
authors.forename: Richard
authors.initials: R
authors.lastname: Channick
authors.forename: David
authors.initials: D
authors.lastname: Badesch
authors.forename: Barry K
authors.initials: BK
authors.lastname: Rayburn
authors.forename: Robin
authors.initials: R
authors.lastname: Flinchbaugh
authors.forename: Jeff
authors.initials: J
authors.lastname: Sigman
authors.forename: Carl
authors.initials: C
authors.lastname: Arneson
authors.forename: Roger
authors.initials: R
authors.lastname: Jeffs
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011788:Quality of Life; D012720:Severity of Illness Index; D013607:Tablets; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D013607:Tablets; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol