title: Tadalafil for the treatment of pulmonary arterial hypertension: a double-blind 52-week uncontrolled extension study.
abstract: OBJECTIVE
  The aim of this study was to evaluate the long-term safety and durability of efficacy of tadalafil for pulmonary arterial hypertension.
  
  
  BACKGROUND
  Tadalafil is an oral phosphodiesterase-5 inhibitor approved for PAH treatment. In the multicenter, placebo-controlled, randomized, 16-week PHIRST (Pulmonary Arterial Hypertension and Response to Tadalafil) study, tadalafil 40 mg improved exercise capacity and delayed clinical worsening.
  
  
  METHODS
  Eligible patients from PHIRST received once-daily tadalafil 20 mg (T20 mg) or 40 mg (T40 mg) (n = 357) in the double-blind, 52-week, uncontrolled extension study (PHIRST-2); 293 patients completed PHIRST-2. Durability of efficacy was explored using the 6-min walk distance (6MWD) test. Clinical worsening and changes in World Health Organization functional class were evaluated.
  
  
  RESULTS
  The safety profile of tadalafil in PHIRST-2 was similar to that in PHIRST, with typical phosphodiesterase-5 inhibitor adverse events. The 6MWDs achieved in PHIRST for the subset of patients receiving T20 mg and T40 mg in both PHIRST and PHIRST-2 (406 ± 67 m [n = 52] and 413 ± 81 m [n = 59] at PHIRST-2 enrollment, respectively) were maintained at PHIRST-2 completion (415 ± 80 m [n = 51] and 410 ± 78 m [n = 59], respectively). Numerically fewer patients who were on T40 mg in PHIRST and PHIRST-2 experienced World Health Organization functional class deterioration (6% [n = 5]) compared with those randomized to T20 mg (9% [n = 7]) across both studies. Post hoc analyses showed that background bosentan use and higher 6MWD at PHIRST baseline were associated with fewer clinical worsening events.
  
  
  CONCLUSIONS
  Long-term treatment with tadalafil was well tolerated in patients with pulmonary arterial hypertension. In patients receiving either T20 mg or T40 mg, the improvements in 6MWD demonstrated in the 16-week PHIRST study appeared sustained for up to 52 additional weeks of treatment in PHIRST-2. (Pulmonary Arterial Hypertension and Response to Tadalafil Study; NCT00549302).
authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. roudiz@labiomed.org
authors: Ronald J
authors: RJ
authors: Oudiz
authors: Bruce H
authors: BH
authors: Brundage
authors: Nazzareno
authors: N
authors: Galiè
authors: Hossein Ardeschir
authors: HA
authors: Ghofrani
authors: Gerald
authors: G
authors: Simonneau
authors: Fady T
authors: FT
authors: Botros
authors: Melanie
authors: M
authors: Chan
authors: Anthony
authors: A
authors: Beardsworth
authors: Robyn J
authors: RJ
authors: Barst
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077300:Bosentan; D002243:Carbolines / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D013449:Sulfonamides / Q000627:therapeutic use; D000068581:Tadalafil; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D013449:Sulfonamides; D014665:Vasodilator Agents; D000068581:Tadalafil; D000077300:Bosentan