Michael Kuntz1, Miguel M Leiva-Juarez2, Suvitesh Luthra3. 1. Massachussets General Hospital, Boston, MA, USA. 2. Department of Pulmonary Medicine, MD Anderson Cancer Center, Houston, TX, USA. 3. Division of Cardiac Surgery, Derriford Hospital, Level 9, Terence Lewis Building, Plymouth, Devon, PL6 8DH, UK. suvitesh.luthra@nhs.net.
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.
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.
Authors: Robyn J Barst; Kamal K Mubarak; Roberto F Machado; Kenneth I Ataga; Raymond L Benza; Oswaldo Castro; Robert Naeije; Namita Sood; Paul S Swerdlow; Mariana Hildesheim; Mark T Gladwin Journal: Br J Haematol Date: 2010-02-17 Impact factor: 6.998
Authors: Robyn J Barst; David Langleben; David Badesch; Adaani Frost; E Clinton Lawrence; Shelley Shapiro; Robert Naeije; Nazzareno Galie Journal: J Am Coll Cardiol Date: 2006-04-24 Impact factor: 24.094
Authors: Nazzareno Galiè; Hossein A Ghofrani; Adam Torbicki; Robyn J Barst; Lewis J Rubin; David Badesch; Thomas Fleming; Tamiza Parpia; Gary Burgess; Angelo Branzi; Friedrich Grimminger; Marcin Kurzyna; Gérald Simonneau Journal: N Engl J Med Date: 2005-11-17 Impact factor: 91.245
Authors: Raymond L Benza; Robyn J Barst; Nazzareno Galie; Adaani Frost; Reda E Girgis; Kristin B Highland; Charlie Strange; Carol M Black; David B Badesch; Lewis Rubin; Thomas R Fleming; Robert Naeije Journal: Chest Date: 2008-07-14 Impact factor: 9.410
Authors: N Galiè; Lj Rubin; Mm Hoeper; P Jansa; H Al-Hiti; Gmb Meyer; E Chiossi; A Kusic-Pajic; G Simonneau Journal: Lancet Date: 2008-06-21 Impact factor: 79.321
Authors: Sulaiman Surie; Herre J Reesink; J Tim Marcus; Mart N van der Plas; Jaap J Kloek; Anton Vonk-Noordegraaf; Paul Bresser Journal: Clin Cardiol Date: 2013-08-27 Impact factor: 2.882
Authors: Polyvios Demetriades; Amir Aziz; Robin Condliffe; Sarah E Bowater; Paul F Clift Journal: BMC Cardiovasc Disord Date: 2017-05-22 Impact factor: 2.298