February 1, 2018European Respiratory Journal196 citationsOpen Access
Macitentan in pulmonary hypertension due to left ventricular dysfunction
Structured PICO
Does macitentan reduce a composite of significant fluid retention or worsening NYHA functional class in patients with pulmonary hypertension due to left heart disease?
P
Population
63 patients with pulmonary hypertension due to left heart disease (PH-LHD) with combined post- and pre-capillary PH (diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance >3WU)
I
Intervention
Macitentan 10 mg for 12 weeks
C
Comparator
Placebo for 12 weeks
O
Outcome
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 (12 weeks)composite
In patients with pulmonary hypertension due to left heart disease, macitentan did not significantly improve clinical or hemodynamic outcomes and was associated with numerically more fluid retention and adverse events.
Abstract
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.