Dept of Cardiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
Dept of Respiratory Diseases, KU Leuven - University Hospitals of Leuven, Leuven, Belgium.
Eur Respir J. 2018 Feb 7;51(2). doi: 10.1183/13993003.01886-2017. Print 2018 Feb.
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, 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·m) 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 placebo.Macitentan-treated patients were quantitatively more likely to experience significant fluid retention placebo. Macitentan resulted in no significant changes in any exploratory end-points.
MELODY-1 研究评估了马西替坦治疗左心疾病（PH-LHD）相关肺动脉高压的疗效，该研究纳入了合并前、后毛细血管 PH 的患者。63 名 PH-LHD 患者存在舒张末期压力梯度≥7mmHg 和肺血管阻力（PVR）>3WU，被随机分配至马西替坦 10mg 组（n=31）或安慰剂组（n=32），治疗 12 周。主要终点评估了从基线到治疗结束时因液体超负荷或给予静脉利尿剂而导致的体重增加≥5%或≥5kg，或纽约心脏协会（NYHA）心功能分级恶化的复合终点。探索性终点包括第 12 周时 N 末端脑利钠肽前体（NT-proBNP）和血液动力学的变化。7 名马西替坦治疗患者和 4 名安慰剂治疗患者出现明显的液体潴留/心功能恶化；治疗差异为 10.08%（95%CI-15.07-33.26；p=0.34）。该差异由液体潴留成分驱动，在第一个月内即表现明显。第 12 周时，与安慰剂组相比，马西替坦组的 PVR、平均右心房压或肺动脉楔压无变化；心指数（治疗效果 0.4（95%CI0.1-0.7）L·min·m）略有增加，NT-proBNP 降低（0.77（0.55-1.08））。马西替坦 安慰剂的不良事件和严重不良事件发生频率更高。马西替坦治疗患者更有可能出现明显的液体潴留，而安慰剂组则无。马西替坦治疗并未引起任何探索性终点的显著变化。
