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

Abstract

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. Clinicaltrials.gov registration numbers NCT00310830, NCT00313196, NCT00360087.

• Authors: Robyn J Barst, Kamal K Mubarak, Roberto F Machado, Kenneth I Ataga, Raymond L Benza, Oswaldo Castro, Robert Naeije, Namita Sood, Paul S Swerdlow, Mariana Hildesheim, Mark T Gladwin, ASSET study group*
• Journal: British journal of haematology (Br J Haematol) Vol. 149 Issue 3 Pg. 426-35 (May 2010) ISSN: 1365-2141 [Electronic] England
• PMID: 20175775 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Sulfonamides
• Bosentan

Topics

• Adult
• Anemia, Sickle Cell (complications, physiopathology)
• Antihypertensive Agents (adverse effects, therapeutic use)
• Bosentan
• Double-Blind Method
• Exercise Test (methods)
• Exercise Tolerance (drug effects)
• Female
• Hemodynamics (drug effects)
• Humans
• Hypertension, Pulmonary (drug therapy, etiology, physiopathology)
• Male
• Middle Aged
• Pulmonary Artery (physiopathology)
• Sulfonamides (adverse effects, therapeutic use)
• Vascular Resistance (drug effects)