Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first-line oral bosentan compared with an historical cohort of patients started on i.v. epoprostenol

Olivier Sitbon ^1*, Vallerie V McLaughlin ², David B Badesch ³, Robyn J Barst ⁴, Carol Black ⁵, Nazzareno Galiè ⁶, Marc Humbert ¹, Maurizio Rainisio ⁷, Lewis J Rubin ⁸ and Gérald Simonneau ¹

¹ Hopital Antoine Beclere, University Paris-Sud, France
² University of Michigan, Ann Arbor, United States
³ University of Colorado Health Sciences Center, Denver, United States
⁴ Columbia University College of Physicians and Surgeons, New York, United States
⁵ Royal College of Physicians, London, United Kingdom
⁶ University of Bologna, Italy
⁷ Actelion Pharmaceuticals Ltd, Switzerland
⁸ Universityof California, San Diego, United States

^* To whom correspondence should be addressed. E-mail: olivier.sitbon{at}abc.ap-hop-paris.fr.

Accepted 3 July 2005

Abstract

Background: The oral, dual endothelin receptor antagonist bosentan improves exercise capacity and delays clinical worsening in patients with pulmonary arterial hypertension, but its use could delay starting intravenous epoprostenol, a life-saving therapy.

Methods: Survival in patients with functional class III idiopathic pulmonary arterial hypertension treated with bosentan in clinical trials was compared with historical data from similar patients treated with epoprostenol in the clinic. Statistical methods were used to adjust for possible underlying differences between the two groups.

Results: Baseline factors for the 139 bosentan- and 346 epoprostenol-treated patients suggested that the epoprostenol cohort had more severe disease, i.e., lower cardiac index (2.01 vs 2.39 L/min/m²). After 1 and 2 years, Kaplan-Meier survival estimates were 97% and 91%, respectively, in the bosentan cohort and 91% and 84% in the epoprostenol cohort. Cox regression analyses adjusting for differences in baseline factors showed a greater probability of death in the epoprostenol cohort (hazard ratio 2.2 with 95% confidence interval of 1.2-4.0 in the model adjusted for hemodynamics). Alternate regression analyses and analyses to adjust for different data collection dates gave consistently similar results. When matched cohorts of 83 patients each were selected, survival estimates were similar. In the bosentan cohort, 87% and 75% of patients followed 1 and 2 years remained on monotherapy.

Conclusions: No evidence was found to suggest that initial therapy with oral bosentan, followed by other treatment if needed, adversely affected long-term outcome compared with initial intravenous epoprostenol in class III idiopathic PAH patients.

Keywords: bosentan, endothelin, epoprostenol, hypertension, pulmonary, survival analysis

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