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 treatment.
Methods: Survival in patients with functional class III idiopathic pulmonary arterial hypertension (PAH) 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 patients treated with bosentan and the 346 treated with epoprostenol suggested that the epoprostenol cohort had more severe disease—that is, a lower cardiac index (2.01 v 2.39 l/min/m2) and higher pressures and resistance. Kaplan-Meier survival estimates after 1 and 2 years 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 (95% confidence interval 1.2 to 4.0) in the model adjusted for haemodynamics). Alternative 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 for 1 and 2 years, respectively, remained on monotherapy.
Conclusions: No evidence was found to suggest that initial treatment with oral bosentan, followed by or with the addition of other treatment if needed, adversely affected the long term outcome compared with initial intravenous epoprostenol in patients with class III idiopathic PAH.
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Selected References
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- Badesch D. B., Tapson V. F., McGoon M. D., Brundage B. H., Rubin L. J., Wigley F. M., Rich S., Barst R. J., Barrett P. S., Kral K. M. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med. 2000 Mar 21;132(6):425–434. doi: 10.7326/0003-4819-132-6-200003210-00002. [DOI] [PubMed] [Google Scholar]
- Barst R. J., Rubin L. J., Long W. A., McGoon M. D., Rich S., Badesch D. B., Groves B. M., Tapson V. F., Bourge R. C., Brundage B. H. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996 Feb 1;334(5):296–301. doi: 10.1056/NEJM199602013340504. [DOI] [PubMed] [Google Scholar]
- Channick R. N., Simonneau G., Sitbon O., Robbins I. M., Frost A., Tapson V. F., Badesch D. B., Roux S., Rainisio M., Bodin F. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001 Oct 6;358(9288):1119–1123. doi: 10.1016/S0140-6736(01)06250-X. [DOI] [PubMed] [Google Scholar]
- D'Alonzo G. E., Barst R. J., Ayres S. M., Bergofsky E. H., Brundage B. H., Detre K. M., Fishman A. P., Goldring R. M., Groves B. M., Kernis J. T. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991 Sep 1;115(5):343–349. doi: 10.7326/0003-4819-115-5-343. [DOI] [PubMed] [Google Scholar]
- McLaughlin V. V., Sitbon O., Badesch D. B., Barst R. J., Black C., Galiè N., Rainisio M., Simonneau G., Rubin L. J. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J. 2005 Feb;25(2):244–249. doi: 10.1183/09031936.05.00054804. [DOI] [PubMed] [Google Scholar]
- McLaughlin Vallerie V., Shillington Alicia, Rich Stuart. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002 Sep 17;106(12):1477–1482. doi: 10.1161/01.cir.0000029100.82385.58. [DOI] [PubMed] [Google Scholar]
- Rubin Lewis J., Badesch David B., Barst Robyn J., Galie Nazzareno, Black Carol M., Keogh Anne, Pulido Tomas, Frost Adaani, Roux Sebastien, Leconte Isabelle. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002 Mar 21;346(12):896–903. doi: 10.1056/NEJMoa012212. [DOI] [PubMed] [Google Scholar]
- Sitbon Olivier, Badesch David B., Channick Richard N., Frost Adaani, Robbins Ivan M., Simonneau Gérald, Tapson Victor F., Rubin Lewis J. Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest. 2003 Jul;124(1):247–254. doi: 10.1378/chest.124.1.247. [DOI] [PubMed] [Google Scholar]
- Sitbon Olivier, Humbert Marc, Nunes Hilario, Parent Florence, Garcia Gilles, Hervé Philippe, Rainisio Maurizio, Simonneau Gérald. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol. 2002 Aug 21;40(4):780–788. doi: 10.1016/s0735-1097(02)02012-0. [DOI] [PubMed] [Google Scholar]
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