A Cochrane review included 12 studies with a total of 1 471 subjects. The studies were of relatively short duration (12 weeks to 6 months). Six studies compared a non-selective endothelin receptor antagonist (ERA; bosentan) with placebo, one compared bosentan with sildenafil (a phosphodiesterase inhibitor), and five compared selective ERAs (sitaxsentan or ambrisentan) with placebo. After treatment, patients treated with endothelin receptor antagonists could walk on average 33.7 metres (95% CI 24.9 to 42.5 metres) further than those treated with placebo in a 6 minute walk test. Endothelin receptor antagonists improved more patients WHO/NYHA functional class status than placebo (OR 1.60, 95% CI 1.20 to 2.14), and reduced the odds of functional class deterioration compared to placebo (OR 0.26, 95% CI 0.16 to 0.42). There was a trend for endothelin receptor antagonists to reduce mortality (OR 0.57, 95% CI 0.26 to 1.24) that did not reach statistical significance, and limited data suggest that endothelin receptor antagonists improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients. A subgroup analysis comparing participants with idiopathic pulmonary artery hypertension (PAH) versus participants with PAH related to other conditions was not conducted due to lack of sufficient information. Most evidence comes from studies in patients with the idiopathic form of the disease. The most severe side effect, hepatic toxicity, was not common (54/618 ERA vs. 14/382 placebo; OR 1.94, 95% CI 0.67 to 5.65).
Note: Several cases of irreversible liver failure caused by sitaxsentan have been reported that led to license holder for sitaxsentan to withdraw the product from all markets worldwide.
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