Systematic Review of Randomized Controlled Trials of Endothelin Receptor Antagonists for Pulmonary Arterial Hypertension
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There are currently three Food and Drug Administration approved endothelin receptor antagonists (ERAs): bosentan, ambrisentan, and macitentan. There is a growing body of evidence that demonstrates the beneficial effects of ERAs in patients with pulmonary arterial hypertension (PAH).
To compare the available evidence from randomized clinical trials for specific outcomes of different endothelin antagonists for the treatment of PAH.
A multi-database search of randomized controlled trials up to March 15, 2016 was conducted for those that would measure functional parameters of patients with PAH treated with ERA monotherapy versus placebo. Studies that analyzed 6-min walking distance, pulmonary vascular resistance, pulmonary arterial pressure, or WHO functional status were incorporated for analysis. A total of 15 trials and 2 subanalyses were compiled and quality and abovementioned outcomes were compared among studies.
A constant decrease in pulmonary vascular resistance and pulmonary arterial pressure was globally reported among the different studies, resulting in increased 6-min walking distance and functional status compared to placebo.
Although this evidence clearly shows the benefit of ERAs, studies, which compare ERAs against one another and with other therapies for progressive PAH, have been lacking. Larger and longer studies are necessary to define the role of ERAs as standalone agents and in combination therapies.
KeywordsPulmonary arterial hypertension Bosentan Endothelin antagonists Macitentan Sitaxsentan Ambrisentan
6-min walking distance
Ambrisentan in pulmonary arterial hypertension efficacy study
Atrial septal defect
Bosentan randomized trial of endothelin antagonist therapy
Chronic thromboembolic pulmonary hypertension
Endothelin antagonist trial in mildly symptomatic pulmonary arterial hypertension patients
Endothelin receptor antagonist
Pulmonary arterial hypertension
Pulmonary artery pressure
Pulmonary vascular resistance
Randomized controlled trial
Study with a endothelin receptor antagonist in pulmonary arterial hypertension to improve clinical outcome
Sitaxsentan to relieve impaired exercise
Ventricular septal defect
Compliance with Ethical Standards
Conflict of interest
The authors report no conflict of interest related to the work performed for this manuscript.
- 11.Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA et al (2008) Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 117:3010–3019CrossRefPubMedGoogle Scholar
- 13.Berger RMF, Beghetti M, Galie N, Gatzoulis MA, Granton J, Lauer A et al (2010) Atrial septal defects versus ventricular septal defects in BREATHE-5, a placebo-controlled study of pulmonary arterial hypertension related to eisenmenger’s syndrome: a subgroup analysis. Int J Cardiol 144:373–378CrossRefPubMedGoogle Scholar
- 19.Formulary (Internet) (2011) Pfizer voluntarily withdraws sitaxsentan from the market worldwide and halts ongoing clinical trials. http://formularyjournal.modernmedicine.com/. Cited 2 Nov 2013
- 20.FDA Label (Internet) (2013)Highlights of prescribing information: Letairis (ambrisentan). www.accessdata.fda.gov. Cited 2 Aug 2013; Revised 10/2012
- 21.FDA Label (Internet) (2013)Highlights of prescribing information: Tracleer (bosentan). www.accessdata.fda.gov.Cited 2 Aug 2013; Revised: 10/2012
- 22.FDA Label (Internet) (2013)Highlights of prescribing information: Opsumit (macitentan). www.accessdata.fda.gov. Cited 27 Oct 2013; Revised: October 2013