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.

Dept of Cardiology Hôpital Erasme Université Libre de Bruxelles Brussels 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 Clinical Research Actelion Clinical Research Inc Cherry Hill NJ USA

Dept of Global Clinical Science and Epidemiology Actelion Pharmaceuticals Ltd Allschwil Switzerland

Dept of Internal Medicine 1 Cardiology University Hospital Olomouc Olomouc Czech Republic

Dept of Respiratory Diseases KU Leuven University Hospitals of Leuven Leuven Belgium

Division of Pulmonary and Critical Care Medicine University of California San Diego La Jolla CA USA

Eur Respir J. 2018 Feb 7;51(2):1702589. doi: 10.1183/13993003.02589-2017. PubMed

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