title: Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension.
abstract: In pulmonary arterial hypertension (PAH), adding oral sildenafil to intravenous epoprostenol improved 6-minute walk distance (6MWD) and hemodynamics and delayed time to clinical worsening in a 16-week randomized, placebo-controlled trial (Pulmonary Arterial Hypertension Combination Study of Epoprostenol and Sildenafil [PACES-1]).
  
  
  
  Patients completing PACES-1 could receive sildenafil (titrated to 80 mg, three times daily, as tolerated) in an open-label extension study (PACES-2) for ≥ 3 years; additional therapy was added according to investigator judgment. Survival and changes from PACES-1 baseline in World Health Organization Functional Class and 6MWD were captured.
  
  
  
  In an open-label setting, 6MWD, an effort-dependent outcome measure, was known to have improved or to have been maintained in 59%, 44%, and 33% of patients at 1, 2, and 3 years, respectively; functional class was known to have improved or to have been maintained in 73%, 59%, and 46%. At 3 years, 66% of patients were known to be alive, 24% were known to have died, and 10% were lost to follow-up. Patients with PACES-1 baseline 6MWD < 325 meters without 6MWD improvement during the first 20 weeks of sildenafil treatment subsequently had poorer survival.
  
  
  
  Although reliable assessments of safety and efficacy require a long-term randomized trial, the addition of sildenafil to background intravenous epoprostenol therapy appeared generally to be well tolerated in PAH patients.
authors.affiliation: University Paris-Sud, National Reference Center for Severe Pulmonary Hypertension, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France. Electronic address: gerald.simonneau@bct.aphp.fr.
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, California.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.affiliation: Institute of Cardiology, Bologna University Hospital, Bologna, Italy.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.affiliation: Division of Pediatric Cardiology, Columbia University, New York, New York.
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.affiliation: Department of Medicine, Section of Pulmonary and Critical Care, Baylor College of Medicine, Houston, Texas.
authors.forename: Adaani
authors.initials: A
authors.lastname: Frost
authors.affiliation: Pulmonary Hypertension Program, The Christ Hospital, Cincinnati, Ohio.
authors.forename: Peter
authors.initials: P
authors.lastname: Engel
authors.affiliation: Pulmonary Institute, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Mordechai R
authors.initials: MR
authors.lastname: Kramer
authors.affiliation: Pfizer Inc, New York, New York.
authors.forename: Marjana
authors.initials: M
authors.lastname: Serdarevic-Pehar
authors.affiliation: Worldwide Pharmaceutical Operations, Pfizer Ltd, Sandwich, Kent, United Kingdom.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Layton
authors.affiliation: University Paris-Sud, National Reference Center for Severe Pulmonary Hypertension, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, and Cardiology Director, Pulmonary Hypertension Program, University of Colorado Denver, Denver, Colorado.
authors.forename: David B
authors.initials: DB
authors.lastname: Badesch
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate; D011464:Epoprostenol
keywords: clinical trial; epoprostenol; pulmonary arterial hypertension; sildenafil; survival