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scientific articles

Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies

key information

source: British Journal of Haematology

year: 2010

authors: Barst RJ, Mubarak KK, Machado RF, Ataga KI, Benza RL, Castro O, Naeije R, Sood N, Swerdlow PS, Hildesheim M, Gladwin MT


Doppler-defined pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with 40% mortality at 40 months. To assess the effect of bosentan in SCD-PH, two randomized, double-blind, placebo-controlled, 16-week studies were initiated. Safety concerns are particularly relevant in SCD due to comorbid conditions. ASSET-1 and -2 enrolled patients with pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PH), respectively. Haemodynamics and 6-min walk distance (6MWD) were obtained at baseline and week 16. The studies were terminated due to slow site initiation and patient enrolment (n = 26). Bosentan appeared to be well tolerated. Although sample sizes were limited, in ASSET-1 at baseline, 6MWD correlated with cardiac output (CO; P = 0.006) with non-significant inverse correlations between 6MWD and pulmonary vascular resistance (PVR; P = 0.07) and between 6MWD and right atrial pressure (P = 0.08). In ASSET-2 at baseline, there was a non-significant correlation between 6MWD and CO (P = 0.06). Due to limited sample sizes, efficacy endpoints were not analysed. However, in both studies, non-significant increases in CO were observed with bosentan compared to placebo. Similarly, non-significant decreases in PVR were observed with bosentan. Limited data in SCD-PH suggest that a low 6MWD predicts a low CO. Standard-dose bosentan appears to be well tolerated. Further investigation is warranted.

organization: Columbia University

DOI: 10.1111/j.1365-2141.2010.08097.x

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