Bosentan Therapy for Pulmonary Arterial Hypertension

doi:10.1056/NEJMoa012212

A correction has been published: N Engl J Med 2002;346(16):1258.

Volume 346:896-903		March 21, 2002		Number 12

Bosentan Therapy for Pulmonary Arterial Hypertension

Lewis J. Rubin, M.D., David B. Badesch, M.D., Robyn J. Barst, M.D., Nazzareno Galiè, M.D., Carol M. Black, M.D., Anne Keogh, M.D., Tomas Pulido, M.D., Adaani Frost, M.D., Sébastien Roux, M.D., Isabelle Leconte, Ph.D., Michael Landzberg, M.D., Gérald Simonneau, M.D., for the Bosentan Randomized Trial of Endothelin Antagonist Therapy Study Group

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ABSTRACT

Background Endothelin-1 is a potent vasoconstrictor and smooth-musclemitogen. In a preliminary study, the orally administered dualendothelin-receptor antagonist bosentan improved exercise capacityand cardiopulmonary hemodynamics in patients with pulmonaryarterial hypertension. The present trial investigated the effectof bosentan on exercise capacity in a larger number of patientsand compared two doses.

Methods In this double-blind, placebo-controlled study, we randomlyassigned 213 patients with pulmonary arterial hypertension (primaryor associated with connective-tissue disease) to receive placeboor to receive 62.5 mg of bosentan twice daily for 4 weeks followedby either of two doses of bosentan (125 or 250 mg twice daily)for a minimum of 12 weeks. The primary end point was the degreeof change in exercise capacity. Secondary end points includedthe change in the Borg dyspnea index, the change in the WorldHealth Organization (WHO) functional class, and the time toclinical worsening.

Results At week 16, patients treated with bosentan had an improved six-minute walking distance;the mean difference between theplacebo group and the combined bosentan groups was 44 m (95percent confidence interval, 21 to 67; P<0.001). Bosentanalso improved the Borg dyspnea index and WHO functional classand increased the time to clinical worsening.

Conclusions The endothelin-receptor antagonist bosentan is beneficialin patients with pulmonary arterial hypertension and is welltolerated at a dose of 125 mg twice daily. Endothelin-receptorantagonism with oral bosentan is an effective approach to therapyfor pulmonary arterial hypertension.

Source Information

From the Division of Pulmonary and Critical Care Medicine, University of California at San Diego, La Jolla (L.J.R.); the University of Colorado Health Sciences Center, Denver (D.B.B.); Babies and Children's Hospital, Columbia Presbyterian Medical Center, New York (R.J.B.); the Università di Bologna, Bologna, Italy (N.G.); the Royal Free Hospital School of Medicine, London (C.M.B.); St. Vincent's Hospital, Darlinghurst, Australia (A.K.); the Instituto Nacional de Cardiología, Mexico City, Mexico (T.P.); Baylor College of Medicine and Methodist Hospital, Houston (A.F.); Actelion, Allschwil, Switzerland (S.R., I.L.); Children's Hospital and Harvard Medical School, Boston (M.L.); and Hôpital Antoine Béclère, Clamart, France (G.S.).

Address reprint requests to Dr. Rubin at the Division of Pulmonary and Critical Care Medicine, University of California at San Diego, 9300 Campus Point Dr., M/C 7372, La Jolla, CA 92037-1330, or at ljrubin{at}ucsd.edu.

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Bosentan for Pulmonary Hypertension
Pereira B. N., Salvi S., Dietrich C. G., Geier A., Lammert F., Rubin L. J., Galiè N., Simonneau G., the Bosentan Randomized Trial of Endothelin Antagonist Therapy Study Investigators
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N Engl J Med 2002; 347:292-294, Jul 25, 2002. Correspondence

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