Article

Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: A randomised placebo-controlled study

Duke University, Durham, North Carolina, United States
The Lancet (Impact Factor: 45.22). 10/2001; 358(9288):1119-23. DOI: 10.1016/S0140-6736(01)06250-X
Source: PubMed

ABSTRACT 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.
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.
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.
Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.

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    • "Sildenafil improves exercise capacity and reduces PAP [6]. Bosentan reduces PAP and improves exercise capacity as well as functional class in patients with PAH [7] [8]. A combination of a PDE-5 inhibitor and endothelin-1 receptor antagonist is standard therapy for advanced PAH [9]. "
    Pharmacology & Pharmacy 12/2013; 04(07):542-548. DOI:10.4236/pp.2013.47078
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    • "The currently used parameters are far from perfect, especially in young children with PAH. The World Health Organization functional class (WHO-functional class) and 6-minute walk distance (6-MWD) are recognized as valuable prognostic parameters that are recommended to be used in goal-oriented treatment strategies in adult PAH-patients [4] [5] [6] [7]. "
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    International journal of cardiology 01/2013; 168(2):1370-7. DOI:10.1016/j.ijcard.2012.12.080 · 6.18 Impact Factor
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    • " shown previously ( Aldashev et al . , 2002 ) . Taken into account that ET - 1 plays an important role in high altitude - related illness , we decided to investigate the effect of dual ET receptors blocker on PAP in highlanders with HAPH . Bosentan is known to reduce PAP , and improve ex - ercise capacity and quality of life in patients with PAH ( Channick et al . , 2001 ; Rubin et al . , 2002 ) . Modesti and co - authors demonstrated that bosentan effectively attenuates hypoxic pulmonary vasoconstriction in healthy subjects dur - ing acclimatization to high altitude , but was also associated with reduction of urinary volume and free water clearance ( Modesti et al . , 2006 ) . In another study , a sing"
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