Endothelin Receptor Antagonists for Pulmonary Arterial Hypertension

Summary

A Cochrane review [Abstract] 1 included 17 studies with a total of 3 322 subjects. Most studies were of relatively short duration (12 weeks to 6 months). Nine studies compared a non-selective endothelin receptor antagonist (ERA; bosentan or macitentan) with placebo, 7 compared selective ERAs (sitaxsentan or ambrisentan) with placebo, and one study compared bosentan with sildenafil (a phosphodiesterase type 5 (PDE5) inhibitor). Three studies tested the efficacy of combination therapy versus monotherapy.

After treatment, patients treated with ERAs could walk on average 25.06 metres (95% CI 17.13 to 32.99 metres) further than those treated with placebo in a 6 minute walk test (14 studies, n=2 739). ERAs improved more patients' WHO functional class than placebo (OR 1.41, 95% CI 1.16 to 1.70; 15 studies, n=3 060), and reduced the odds of functional class deterioration compared to placebo (OR 0.43, 95% CI 0.26 to 0.72; 13 studies, n=2 347). There was a trend for ERAs to reduce mortality (OR 0.78, 95% CI 0.58 to 1.07; 12 studies, n=2 889) that did not reach statistical significance, and pooled data suggested that ERAs improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients. The most severe side effect, hepatic toxicity (OR 1.88, 95% CI 0.91 to 3.90), was not common, but may be increased by ERA treatment from 37 to 67 (95% CI 34 to 130) per 1000 over 25 weeks of treatment. Subgroup analyses comparing selective and non-selective ERAs did not detect any clear subgroup differences for any outcome with the exception of mean pulmonary artery pressure.