Endothelin receptor antagonists for pulmonary arterial hypertension

Pulmonary arterial hypertension is a devastating disease that leads to right heart failure and premature death. Endothelin receptor antagonists are a class of strong vasodilators (medications that open (dilate) blood vessels) capable of stopping the process of cell division, which could dilate and result in a favourable pulmonary arterial structural alteration. Endothelin receptor antagonists have shown efficacy in the treatment of pulmonary arterial hypertension.

The review included 17 randomised controlled trials involving a total of 3322 participants. Most trials were of relatively short duration (12 weeks to six months). Sixteen trials were placebo‐controlled, and of these nine investigated a non‐selective ERA and seven a selective ERA.

The review evaluated two comparisons in the review: ERA versus placebo and ERA versus phosphodiesterase type 5 (PDE5) inhibitor. This summary focuses on the placebo‐controlled trials only and presents the pooled results of selective and non‐selective ERAs

Key findings:

  • For people with pulmonary arterial hypertension with WHO functional class II and III, compared with placebo endothelin receptor antagonists probably:
    • increase exercise capacity
    • improve WHO functional class
    • prevent WHO functional class deterioration,
    • result in favourable changes in cardiopulmonary haemodynamic
    • However, they are less effective in reducing dyspnoea and mortality.
  • Efficacy data were strongest in those with idiopathic pulmonary hypertension.
  • The irreversible liver failure caused by sitaxsentan and its withdrawal from global markets emphasise the importance of hepatic monitoring in people treated with ERAs.
  • The question of the effects of ERAs on pulmonary arterial hypertension has now likely been answered.
  • The combined use of ERAs and phosphodiesterase inhibitors may provide more benefit in pulmonary arterial hypertension; however, this needs to be confirmed in future studies.
  • Overall, the evidence presented is of moderate certainty due to the high occurrence of missing data.
  • Subgroup analyses compared selective and non‐selective ERAs, and with the exception of mean pulmonary artery pressure, did not detect any clear subgroup differences for any outcome

The review is current to 4 November 2020.

This summary is based on the abstract of the review and was prepared by Emma Dennett.

The full review can be found here