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Lung

, Volume 194, Issue 5, pp 723–732 | Cite as

Systematic Review of Randomized Controlled Trials of Endothelin Receptor Antagonists for Pulmonary Arterial Hypertension

  • Michael Kuntz
  • Miguel M. Leiva-Juarez
  • Suvitesh Luthra
Article

Abstract

Background

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).

Objectives

To compare the available evidence from randomized clinical trials for specific outcomes of different endothelin antagonists for the treatment of PAH.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Pulmonary arterial hypertension Bosentan Endothelin antagonists Macitentan Sitaxsentan Ambrisentan 

Abbreviations

6MWD

6-min walking distance

ARIES

Ambrisentan in pulmonary arterial hypertension efficacy study

ASD

Atrial septal defect

BREATHE

Bosentan randomized trial of endothelin antagonist therapy

CTEPH

Chronic thromboembolic pulmonary hypertension

EARLY

Endothelin antagonist trial in mildly symptomatic pulmonary arterial hypertension patients

ERA

Endothelin receptor antagonist

FC

Functional class

NO

Nitric oxide

PAH

Pulmonary arterial hypertension

PAP

Pulmonary artery pressure

PVR

Pulmonary vascular resistance

RCT

Randomized controlled trial

SERAPHIN

Study with a endothelin receptor antagonist in pulmonary arterial hypertension to improve clinical outcome

STRIDE

Sitaxsentan to relieve impaired exercise

VSD

Ventricular septal defect

Notes

Compliance with Ethical Standards

Conflict of interest

The authors report no conflict of interest related to the work performed for this manuscript.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Michael Kuntz
    • 1
  • Miguel M. Leiva-Juarez
    • 2
  • Suvitesh Luthra
    • 3
  1. 1.Massachussets General HospitalBostonUSA
  2. 2.Department of Pulmonary MedicineMD Anderson Cancer CenterHoustonUSA
  3. 3.Division of Cardiac SurgeryDerriford HospitalPlymouthUK

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