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Eur Respir J. 2018 Feb 7;51(2). pii: 1701886. doi: 10.1183/13993003.01886-2017. Print 2018 Feb.

Macitentan in pulmonary hypertension due to left ventricular dysfunction.

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Dept of Cardiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
Dept of Respiratory Diseases, KU Leuven - University Hospitals of Leuven, Leuven, Belgium.
Dept of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
Dept of Clinical Development - Biostatistics, Actelion Pharmaceuticals Italia, Imperia, Italy.
Dept of Internal Medicine I - Cardiology, University Hospital Olomouc, Olomouc, Czech Republic.
Dept of Global Clinical Science & Epidemiology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Dept of Clinical Research, Actelion Clinical Research Inc., Cherry Hill, NJ, USA.
Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA, USA.


The MELODY-1 study evaluated macitentan for pulmonary hypertension because of left heart disease (PH-LHD) in patients with combined post- and pre-capillary PH.63 patients with PH-LHD and diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance (PVR) >3WU were randomised to macitentan 10 mg (n=31) or placebo (n=32) for 12 weeks. The main end-point assessed a composite of significant fluid retention (weight gain ≥5% or ≥5 kg because of fluid overload or parenteral diuretic administration) or worsening in New York Heart Association functional class from baseline to end of treatment. Exploratory end-points included changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and haemodynamics at week 12.Seven macitentan-treated and four placebo-treated patients experienced significant fluid retention/worsening functional class; treatment difference, 10.08% (95% CI -15.07-33.26; p=0.34). The difference, driven by the fluid retention component, was apparent within the first month. At week 12, versus placebo, the macitentan group showed no change in PVR, mean right atrial pressure or pulmonary arterial wedge pressure; a non-significant increase in cardiac index (treatment effect 0.4 (95% CI 0.1-0.7) L·min-1·m-2) and decrease in NT-proBNP (0.77 (0.55-1.08)) was observed. Adverse events and serious adverse events were numerically more frequent with macitentan versus placebo.Macitentan-treated patients were quantitatively more likely to experience significant fluid retention versus placebo. Macitentan resulted in no significant changes in any exploratory end-points.

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