title: Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: the SUPER-2 study.
abstract: BACKGROUND
  The long-term safety and tolerability of sildenafil treatment of pulmonary arterial hypertension (PAH) were assessed.
  
  
  METHODS
  Two hundred fifty-nine of 277 randomized and treated patients completed a 12-week, double-blind, placebo-controlled trial (SUPER-1 [Sildenafil Use in Pulmonary Arterial Hypertension]) of oral sildenafil in treatment-naive patients with PAH (96% functional class II/III) and entered an open-label uncontrolled extension study (SUPER-2) that continued until the last patient completed 3 years of sildenafil treatment. Patients titrated to sildenafil 80 mg tid; one dose reduction for tolerability was allowed during the titration phase.
  
  
  RESULTS
  The median duration of sildenafil treatment across SUPER-1 and SUPER-2 was 1,242 days (range, 1-1,523 days); 170 patients (61%) completed both studies, and 89 patients discontinued from SUPER-2. After 3 years, 87% of 183 patients on treatment were receiving sildenafil 80 mg tid. Of patients remaining under follow-up, 3%, 10%, and 18% were receiving a second approved PAH therapy at 1, 2, and 3 years, respectively. At 3 years post-SUPER-1 baseline, 127 patients had an increased 6-min walk distance (6MWD); 81 improved and 86 maintained functional class. Most adverse events were of mild or moderate severity. At 3 years, 53 patients had died (censored, n = 37). Three-year estimated survival rate was 79%; if all censored patients were assumed to have died, 3-year survival rate was 68%. No deaths were considered to be treatment related.
  
  
  CONCLUSIONS
  Long-term treatment of PAH initiated as sildenafil monotherapy was generally well tolerated. After 3 years, the majority of patients (60%) who entered the SUPER-1 trial improved or maintained their functional status, and 46% maintained or improved 6MWD.
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA. Electronic address: ljrubin@ucsd.edu.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.affiliation: Department of Medicine, University of Colorado Denver, Denver, CO.
authors.forename: David B
authors.initials: DB
authors.lastname: Badesch
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.affiliation: Institute of Cardiology, University of Bologna, Bologna, Italy.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.affiliation: Centre des Maladies Vasculaires Pulmonaires, Hôpital Antoine Béclère, Clamart Cedex, France.
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
authors.affiliation: Medical Clinic II/V, University Hospital Giessen and Marburg GmbH, Justus-Liebig-University, Giessen, Germany.
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Pfizer Global Research Division, Pfizer Ltd, Sandwich, England.
authors.forename: Michael
authors.initials: M
authors.lastname: Oakes
authors.affiliation: Pfizer Global Research Division, Pfizer Ltd, Sandwich, England.
authors.forename: Gary
authors.initials: G
authors.lastname: Layton
authors.affiliation: Pfizer Global Research Division, Pfizer Ltd, Sandwich, England.
authors.forename: Marjana
authors.initials: M
authors.lastname: Serdarevic-Pehar
authors.affiliation: Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Vallerie V
authors.initials: VV
authors.lastname: McLaughlin
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D016016:Proportional Hazards Models; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D010919:Placebos; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate