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 five categories according to Venice classification: (1) Idiopathic PAH; (2) Familial PAH; (3) PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts, portal hypertension, HIV infection, drugs and toxins or other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy); (4) PAH associated with significant venous or capillary involvement, which includes pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH); (5) Persistent pulmonary hypertension of the newborn. PAH can also be secondary to chronic hypoxic lung disease as part of the "cor-pulmonale" syndrome, and also secondary to left sided heart disease, but these conditions are usually distinguished from those listed here.
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 2005.
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: In this updated version of the review, we added two RCTs. Altogether, five RCTs met the entry criteria of the review (reporting eight group comparisons). The studies were of short duration (12-16 weeks), recruiting a total of 482 participants. Three studies compared a non-selective ERA (bosentan) with placebo, one compared bosentan with sildenafil (a phosphodiesterase inhibitor) , 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 mainly idiopathic PAH. The effect of ERAs on mortality was not significant. The most severe side effect, hepatic toxicity, was not common.
Authors' conclusions: ERAs in conjunction with conventional therapy over 12 to 16 weeks can improve exercise capacity, Borg dyspnoea scores and several cardiopulmonary haemodynamics variables in patients mainly with idiopathic PAH. The data on mortality do not currently show a benefit of this class of drugs on this endpoint. Additional assessment of this outcome is important in order to establish whether there is evidence that ERAs have an impact on the risk of death. Longer studies are required.