Published ahead of print on March 4, 2005, doi:10.1164/rccm.200410-1411OC
American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 1292-1297, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200410-1411OC
Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) Study
Martin R. Wilkins,
Gideon A. Paul*,
Julian W. Strange*,
Nina Tunariu,
Wendy Gin-Sing,
Winston A. Banya,
Mark A. Westwood,
Alexander Stefanidis,
Leong L. Ng,
Dudley J. Pennell,
Raad H. Mohiaddin,
Petros Nihoyannopoulos and
J. Simon R. Gibbs
Experimental Medicine and Toxicology, and Department of Cardiology, Hammersmith Campus, and CMR Unit, National Heart and Lung Institute, Imperial College London; and Department of Cardiovascular Sciences, Leicester Royal Infirmary, Leicester, United Kingdom
Correspondence and requests for reprints should be addressed to M. R. Wilkins, M.D., F.R.C.P., Experimental Medicine and Toxicology, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK. E-mail: m.wilkins{at}imperial.ac.uk
Rationale: Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the treatment for pulmonary arterial hypertension (PAH). Objective: This study compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the current practice of adding bosentan, an endothelin receptor antagonist. Methods: Twenty-six patients with PAH, idiopathic or associated with connective tissue disease, World Health Organization (WHO) functional class III, were randomized in a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) over 16 weeks. Measurements: Changes in right ventricular (RV) mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac function, brain natriuretic peptide, and Borg dyspnea index. Main Results: When analyzed by intention to treat, there were no significant differences between the two treatment groups. One patient on sildenafil died suddenly. Patients on sildenafil who completed the protocol showed significant changes from baseline, namely, reductions in RV mass (–8.8 g; 95% confidence interval [CI], –2, –16; n = 13, p = 0.015) and plasma brain natriuretic peptide levels (–19.4 fmol · ml–1; 95% CI, –5, –34; p = 0.014) and improvements in 6-minute walk distance (114 m; 95% CI, 67, 160; p = 0.0002), cardiac index (0.3 L · min–1 · m–2; 95% CI, 0.1, 0.4; p = 0.008), and systolic left ventricular eccentricity index (–0.2; 95% CI, –0.02, –0.37; p = 0.031). Bosentan improved 6-minute walk distance (59 m; 95% CI, 29, 89; n = 12, p = 0.001) and cardiac index (0.3; 95% CI, 0.1, 0.4; p = 0.008). Conclusions: Sildenafil added to conventional treatment reduces RV mass and improves cardiac function and exercise capacity in patients with PAH, WHO functional class III. Safety monitoring is important until more experience is obtained.
Key Words: cardiovascular disease • cardiac magnetic resonance • pharmacology
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