Kiely David G, Channick Richard, Flores Dayana, Galiè Nazzareno, MacDonald Gwen, Marcus J Tim, Mitchell Lada, Peacock Andrew, Rosenkranz Stephan, Tawakol Ahmed, Torbicki Adam, Vonk Noordegraaf Anton, Swift Andrew J
Sheffield Pulmonary Vascular Disease Unit and NIHR Biomedical Research Centre, Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK.
Department of Clinical Medicine, University of Sheffield, Sheffield, UK.
ERJ Open Res. 2024 Feb 12;10(1). doi: 10.1183/23120541.00547-2023. eCollection 2024 Jan.
Measures that can detect large treatment effects are important for monitoring therapeutic effectiveness. The 2022 European Society of Cardiology/European Respiratory Society guidelines highlight the importance of imaging in monitoring disease status and treatment response in pulmonary arterial hypertension (PAH). Are the standardised treatment effect sizes (STES) of cardiac magnetic resonance imaging (cMRI) comparable with functional and haemodynamic variables?
REPAIR (ClinicalTrials.gov: NCT02310672) was a prospective, multicentre, single-arm, open-label, 52-week phase 4 study evaluating the effect of macitentan 10 mg, with or without a phosphodiesterase 5 inhibitor (PDE5i), on right ventricular (RV) remodelling, cardiac function and cardiopulmonary haemodynamics. Both cMRI and functional assessments were performed at screening and at weeks 26 and 52; haemodynamic measurements were conducted at screening and week 26. In this analysis, STES were estimated using the parametric Cohen's d and non-parametric Cliff's delta tests.
At week 26, large STES (Cohen's d) were observed for 10 of the 20 cMRI variables assessed, including the prognostic measures of RV and left ventricular stroke volume and RV ejection fraction and the haemodynamic trial end-point, pulmonary vascular resistance; medium STES were observed for 6-min walk distance (6MWD). The STES were consistent in treatment-naïve patients and those escalating therapy and maintained at week 52. Similar results were obtained using the non-parametric Cliff's delta method.
The treatment effect of macitentan, alone or in combination with a PDE5i, was comparable for several cMRI and haemodynamic variables with prognostic value in PAH, and greater than that of 6MWD in patients with PAH, highlighting the emerging relevance of cMRI in PAH.
能够检测到显著治疗效果的指标对于监测治疗效果很重要。2022年欧洲心脏病学会/欧洲呼吸学会指南强调了影像学在监测肺动脉高压（PAH）疾病状态和治疗反应中的重要性。心脏磁共振成像（cMRI）的标准化治疗效应大小（STES）与功能和血流动力学变量是否具有可比性？
REPAIR（ClinicalTrials.gov：NCT02310672）是一项前瞻性、多中心、单臂、开放标签的4期研究，为期52周，评估10 mg马昔腾坦联合或不联合磷酸二酯酶5抑制剂（PDE5i）对右心室（RV）重塑、心脏功能和心肺血流动力学的影响。在筛查时以及第26周和第52周进行cMRI和功能评估；在筛查时和第26周进行血流动力学测量。在本分析中，使用参数化的科恩d检验和非参数化的克里夫δ检验估计STES。
在第26周时，在评估的20个cMRI变量中的10个观察到较大的STES（科恩d），包括RV和左心室每搏量、RV射血分数的预后指标以及血流动力学试验终点肺血管阻力；在6分钟步行距离（6MWD）观察到中等STES。在初治患者和升级治疗的患者中，STES在第52周时保持一致。使用非参数化的克里夫δ方法也获得了类似结果。
马昔腾坦单独或与PDE5i联合使用，对PAH中几个具有预后价值的cMRI和血流动力学变量的治疗效果具有可比性，并且在PAH患者中大于6MWD的治疗效果，突出了cMRI在PAH中日益重要的相关性。
