eMedicineLive

Pulmonary arterial hypertension (PAH) is a subset of a larger grouping ‘Pulmonary Hypertension’ and includes the idiopathic PAH, familial PAH and PAH associated with collagen vascular diseases, HIV infection and drugs. Pulmonary arterial Hypertension is defined as mean pulmonary artery pressure greater than 25 mmHg at rest or greater than 30 mmHg with exercise with a pulmonary capillary occlusion pressure of less than 15mmHg and increase in pulmonary vascular resistance greater than 3 wood units in the absence of significant respiratory and cardiac dysfunction.

Historically the prognosis of patients with pulmonary arterial hypertension had been poor. But with the advent of several new therapeutic drugs, the prognosis has greatly improved in recent years. The aim of the drug therapy is to reduce the pulmonary arterial pressure and thereby improve the cardiac output. The drugs that are currently used for pulmonary arterial hypertension include calcium channel antagonists, prostanoids, endothelin receptor antagonists (ERA) and phosphodiesterase inhibitors.

Endothelin receptor antagonists include the drugs Bosentan, Ambrisentan and Sitaxsentan. Endothelin receptor antagonists block the action of endothelin-1(ET-1), a potent vasoconstrictor which is generally elevated in patients with pulmonary arterial hypertension. Two types of endothelin receptors mediate the action of endothelin; ET-A and ET-B.  Bosentan blocks both the receptors while Ambrisentan and Sitaxsentan selectively block the ET-A receptor.  

In a study published in CHEST (Volume 141, Issue 1), investigators pooled data from six randomized trials of endothelin receptor antagonist to analyze the treatment response with regard to the sex and race. Six minute walk test was used as a parameter for assessment of treatment response.

The study revealed that females benefit the most from ERA therapy. Similarly the treatment response is slightly better in whites compared to the blacks. Hence as a group, white females are most likely to respond to therapy with ERAs. The reason for these heterogeneous responses is unclear but authors postulate that these may be related to the differences in the estrogen signaling or right ventricular contractility between sexes. Besides its well known that the concentration of endothelin-1 (ET-1) is higher in males and blacks. It is possible that the currently used doses of ERAs are not sufficient to block the receptors in the presence of high concentrations of ET-1.

The study population had only 6% blacks and only 21% males. The subjects were predominantly white female, which is considered as one of the limitation of the study. Hence more robust studies needed in future to confirm these findings.

On the whole the study suggests that women with pulmonary arterial hypertension experience a greater treatment response with ERA therapy.

Reference
http://www.ncbi.nlm.nih.gov/pubmed/21940766