Sildenafil for Pulmonary Arterial Hypertension Associated with Connective Tissue Disease

DAVID B. BADESCH, NICHOLAS S. HILL, GARY BURGESS, LEWIS J. RUBIN, ROBYN J. BARST, NAZZARENO GALIÈ, and GERALD SIMONNEAU, on behalf of the SUPER Study Group

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.

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. (First Release Nov 1 2007; J Rheumatol 2007;34:2417-22)

Key Indexing Terms:

SILDENAFIL
CONNECTIVE TISSUE DISEASE
SAFETY
PULMONARY ARTERIAL HYPERTENSION
EFFICACY

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From the Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado; Division of Pulmonary, Critical Care and Sleep Medicine, New England Medical Center, Boston, Massachusetts; Division of Pulmonary and Critical Care Medicine, University of California at San Diego, La Jolla, California; Department of Pediatric Cardiology, Columbia Presbyterian Medical Center, New York, New York, USA; Pfizer Global Research and Development, Pfizer Ltd., Sandwich, Kent, UK; Institute of Cardiology, University of Bologna, Bologna, Italy; and the Hôpital Antoine Béclère, Clamart, France.

Supported by Pfizer Ltd., UK.

D.B. Badesch, MD, Professor of Medicine, Divisions of Pulmonary Sciences and Critical Care Medicine and Cardiology, Clinical Director, Pulmonary Hypertension Center, University of Colorado Health Sciences Center; N.S. Hill, MD, Professor of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New England Medical Center; G. Burgess, MD, Pfizer Global Research and Development, Pfizer Ltd.; L.J. Rubin, MD, Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of California at San Diego; R.J. Barst, MD, Professor of Medicine, Department of Pediatric Cardiology, Columbia Presbyterian Medical Center; N. Galiè, MD, Professor of Cardiology, Institute of Cardiology, University of Bologna; G. Simonneau, MD, Professor of Medicine, Hôpital Antoine Béclère.

Address reprint requests to Dr. D.B. Badesch, Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Box C-272, 4200 East Ninth Ave., Denver, CO 80262, USA. E-mail: David.Badesch@uchsc.edu

Accepted for publication August 11, 2007.

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