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Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease
British Journal of Haematology, 10/05/09

Minniti CP et al. – Pulmonary Hypertension is a serious complication of sickle cell disease (SCD), with high morbidity and mortality. Endothelin (ET)–1, a potent vasoconstrictor elevated in SCD, acts through the ET receptors (ETR), ETR–A and ETR–B. Bosentan and ambrisentan are ETR blockers used in primary pulmonary hypertension. These data suggest preliminary evidence for the benefit of bosentan and ambrisentan in pulmonary hypertension in SCD.

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Gregory J. Kato, 10/06/09

Endothelin-1 receptor antagonists are already approved to treat pulmonary hypertension in the general population, but patients with sickle cell disease and pulmonary hypertension pose special therapeutic challenges. In this series of 14 patients with sickle cell disease and pulmonary hypertension proven by right heart catheterization, endothelin receptor antagonists had a side effect profile comparable to the general population. Cardiopulmonary performance was improved by 11%, as indicated by six minute walk distance, with other indicators trending toward improvement as well. This finding is of particular interest in sickle cell disease, because endothelin receptor blockade has been shown to limit hypoxia-induced organ dysfunction in a mouse model of sickle cell disease. There also has been a single anecdotal report of a sickle cell patient with a 28-year history of chronic leg ulcer that healed within 3 weeks of initiating the endothelin receptor blocker bosentan. Endothelin receptor antagonists may have a potential role in the treatment of sickle cell disease and pulmonary hypertension.

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