Macitentan in pulmonary hypertension due to left ventricular dysfunction
Language English Country Great Britain, England Media electronic-print
Document type Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
29437943
DOI
10.1183/13993003.01886-2017
PII: 51/2/1701886
Knihovny.cz E-resources
- MeSH
- Vascular Resistance drug effects MeSH
- Double-Blind Method MeSH
- Ventricular Dysfunction, Left complications MeSH
- Internationality MeSH
- Blood Pressure drug effects MeSH
- Humans MeSH
- Natriuretic Peptide, Brain drug effects metabolism MeSH
- Peptide Fragments drug effects metabolism MeSH
- Hypertension, Pulmonary drug therapy physiopathology MeSH
- Pulmonary Wedge Pressure drug effects MeSH
- Pyrimidines administration & dosage MeSH
- Aged MeSH
- Sulfonamides administration & dosage MeSH
- Walk Test MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- macitentan MeSH Browser
- Natriuretic Peptide, Brain MeSH
- Peptide Fragments MeSH
- pro-brain natriuretic peptide (1-76) MeSH Browser
- Pyrimidines MeSH
- Sulfonamides MeSH
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
References provided by Crossref.org
The neurohormonal basis of pulmonary hypertension in heart failure with preserved ejection fraction
