Endothelin receptor antagonists for pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease, which leads to right heart failure and premature death. Pulmonary arterial hypertension can be classified into two categories: 1) sporadic primary pulmonary hypertension (PPH) or familial PPH and 2) PAH secondary to collagen vascular diseases, congenital systemic to pulmonary shunts, portal hypertension, HIV infection, drugs or toxins, and persistent pulmonary hypertension of the newborn. They have identical pathologic features, a similar clinical course. Endothelin receptor antagonists (ERAs) are a class of potent vasodilators, which could specifically dilate the pulmonary arterial system. OBJECTIVES: To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension. SEARCH STRATEGY: A search was carried out using the CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of August 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised controlled trials involving patients with pulmonary arterial hypertension (PAH) were selected by two reviewers. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies; assessed study quality; and extracted data. We analysed outcomes as continuous and dichotomous data. MAIN RESULTS: We identified three RCTs of short duration (12-16 weeks), recruiting a total of 423 participants. Two studies compared a non-selective ERA (bosentan) with placebo and one compared a selective ERA (sitaxsentan) with placebo. Over a 12-16 week period ERAs improved exercise capacity, improve Borg dyspnoea score, some measures of cardiopulmonary haemodynamics (pulmonary artery pressure, pulmonary vascular resistance, and cardiac index) in symptomatic patients with PAH. The most severe side effect, hepatic toxicity, was not common. AUTHORS' CONCLUSIONS: ERAs in conjunction with conventional therapy over 16 weeks can improve exercise capacity, Borg dyspnoea scores and several cardiopulmonary haemodynamics variables in PAH patients. Longer studies are required.