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Sildenafil for pulmonary arterial hypertension associated with connective tissue disease.

AbstractOBJECTIVE: 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. CONCLUSION: In patients with PAH-CTD, sildenafil improves exercise capacity, hemodynamic measures (at the 20 mg dose), and functional class after 12 weeks of treatment.
AuthorsDavid B Badesch, Nicholas S Hill, Gary Burgess, Lewis J Rubin, Robyn J Barst, Nazzareno Galiè, Gerald Simonneau, SUPER Study Group (Affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. David.Badesch at uchsc.edu)
JournalThe Journal of rheumatology (J Rheumatol) Vol. 34 Issue 12 Pg. 2417-22 (Dec 2007) ISSN: 0315-162X Canada
PMID17985403 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • sildenafil
Topics
  • Adult
  • Aged
  • Connective Tissue Diseases (complications)
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension, Pulmonary (complications, drug therapy)
  • Male
  • Middle Aged
  • Piperazines (administration & dosage)
  • Purines (administration & dosage)
  • Sulfones (administration & dosage)
  • Treatment Outcome
  • Vasodilator Agents (administration & dosage)