title: Sildenafil for pulmonary arterial hypertension associated with connective tissue disease.
abstract: OBJECTIVE
  Pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) is difficult to manage, and has a poor prognosis. The phosphodiesterase-5 inhibitor sildenafil citrate enhances vasodilatation, has antiproliferative effects, and is effective in the treatment of PAH. We examined the efficacy and safety of oral sildenafil in patients with PAH-CTD.
  
  
  METHODS
  In a 12-week, double-blind study (SUPER-1), 278 patients with PAH were randomized to oral placebo, sildenafil 20 mg, sildenafil 40 mg, or sildenafil 80 mg 3 times daily (tid). In a post-hoc subgroup analysis of 84 patients with PAH-CTD, exercise capacity, hemodynamic measures, World Health Organization functional class, and tolerability were assessed.
  
  
  RESULTS
  Forty-five percent of the patients had scleroderma, 23% had systemic lupus erythematosus, and the rest (32%) were categorized as other. Patients were predominantly functional class II (38%) or III (61%) at baseline. Sildenafil-treated patients exhibited mean increases in 6-minute walk distance at Week 12 of 42 m (95% CI 20, 64) for 20 mg, 36 m (95% CI 14, 58) for 40 mg, and 15 m (95% CI -24, 54) for 80 mg, while placebo-treated patients exhibited a mean decrease of 13 m (95% CI -36, 10). Improvement of at least 1 functional class occurred in 29%-42% of sildenafil-treated patients, compared to 5% for placebo. Significant improvements in mean pulmonary arterial pressure and pulmonary vascular resistance were observed with sildenafil 20 mg, and sildenafil was generally well tolerated.
  
  
  CONCLUSIONS
  In patients with PAH-CTD, sildenafil improves exercise capacity, hemodynamic measures (at the 20 mg dose), and functional class after 12 weeks of treatment.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. David.Badesch@uchsc.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Badesch
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hill
authors.forename: Gary
authors.initials: G
authors.lastname: Burgess
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
mesh_terms: D000328:Adult; D000368:Aged; D003240:Connective Tissue Diseases / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate