Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study
- PMID:11597664
- DOI:10.1016/S0140-6736(01)06250-X
Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study
Abstract
Background:Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension. We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in patients with severe pulmonary hypertension.
Methods:In this double-blind, placebo-controlled study, 32 patients with pulmonary hypertension (primary or associated with scleroderma) were randomly assigned to bosentan (62.5mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. The primary endpoint was change in exercise capacity. Secondary endpoints included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO functional class, and withdrawal due to clinical worsening. Analysis was by intention to treat.
Findings:In patients given bosentan, the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by 6 m in those on placebo (difference 76 m [95% CI 12-139], p=0.021). The improvement was maintained for at least 20 weeks. The cardiac index was 1.0 L min(-1) m(-2) (95% CI 0.6-1.4, p<0.0001) greater in patients given bosentan than in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5) with bosentan, but increased by 191 dyn s cm(-5) with placebo (difference -415 [-608 to -221], p=0.0002). Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class. All three withdrawals from clinical worsening were in the placebo group (p=0.033). The number and nature of adverse events did not differ between the two groups.
Interpretation:Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.
Comment in
-
Endothelin-receptor antagonists in pulmonary hypertension.Lancet. 2001 Oct 6;358(9288):1113-4. doi: 10.1016/S0140-6736(01)06298-5. Lancet. 2001. PMID:11597660 没有abstract available.
-
Successful treatment of systemic sclerosis digital ulcers and pulmonary arterial hypertension with endothelin receptor antagonist bosentan.Rheumatology (Oxford). 2003 Jan;42(1):191-3. doi: 10.1093/rheumatology/keg050. Rheumatology (Oxford). 2003. PMID:12509640 没有abstract available.
Similar articles
-
Bosentan therapy for pulmonary arterial hypertension.N Engl J Med. 2002 Mar 21;346(12):896-903. doi: 10.1056/NEJMoa012212. N Engl J Med. 2002. PMID:11907289 Clinical Trial.
-
Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial.Lancet. 2008 Jun 21;371(9630):2093-100. doi: 10.1016/S0140-6736(08)60919-8. Lancet. 2008. PMID:18572079 Clinical Trial.
-
Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial.J Am Coll Cardiol. 2008 Dec 16;52(25):2127-34. doi: 10.1016/j.jacc.2008.08.059. J Am Coll Cardiol. 2008. PMID:19095129 Clinical Trial.
-
Bosentan.Am J Cardiovasc Drugs. 2002;2(5):335-43; discussion 343. doi: 10.2165/00129784-200202050-00006. Am J Cardiovasc Drugs. 2002. PMID:14727963 Review.
-
Bosentan for the treatment of adult pulmonary hypertension.Future Cardiol. 2011 Jan;7(1):19-37. doi: 10.2217/fca.10.114. Future Cardiol. 2011. PMID:21174507 Review.
Cited by269articles
-
Effect of bosentan in pulmonary hypertension development in systemic sclerosis patients with digital ulcers.PLoS One. 2020 Dec 10;15(12):e0243651. doi: 10.1371/journal.pone.0243651. eCollection 2020. PLoS One. 2020. PMID:33301540 Free PMC article.
-
肺动脉高血压Pati管理ents with World Health Organization Functional Class II.Acta Cardiol Sin. 2020 Nov;36(6):583-587. doi: 10.6515/ACS.202011_36(6).20200507A. Acta Cardiol Sin. 2020. PMID:33235413 Free PMC article. Review.
-
Management of Pulmonary Arterial Hypertension.Curr Cardiovasc Risk Rep. 2021;15(1):2. doi: 10.1007/s12170-020-00663-3. Epub 2020 Nov 18. Curr Cardiovasc Risk Rep. 2021. PMID:33224405 Free PMC article. Review.
-
Distribution and relative expression of vasoactive receptors on arteries.Sci Rep. 2020 Sep 21;10(1):15383. doi: 10.1038/s41598-020-72352-5. Sci Rep. 2020. PMID:32958803 Free PMC article.
-
Current and emerging therapeutic approaches to pulmonary hypertension.Rev Cardiovasc Med. 2020 Jun 30;21(2):163-179. doi: 10.31083/j.rcm.2020.02.597. Rev Cardiovasc Med. 2020. PMID:32706206 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical